Treatments/Drug Discovery

 

• More Research Needed on Gabapentin Use for Vulvodynia

  Leo RJ. A Systematic Review of the Utility of Anticonvulsant Pharmacotherapy in the Treatment of Vulvodynia Pain. J Sex Med. 2013 May 16. doi: 10.1111/jsm.12200. [Epub ahead of print]
  Although anticonvulsants are being used to treat vulvodynia, there isn’t enough evidence to justify doing so, according to research from the State University of New York School of Medicine and Biomedical Sciences. A comprehensive search of the medical literature yielded nine published reports on the use of anticonvulsants for vulvodynia, most of which used gabapentin: one open-label trial, six non-experimental studies, and two case reports. There were no systematic investigations comparing the efficacy of different anticonvulsants, and most evidence supporting the use of these drugs was based on descriptive or observational reports. The author noted shortcomings in the reports in terms of study design, and concludes that there is not sufficient evidence to support this treatment and that more research, including randomized controlled trials, are needed.
  
  

• Botox Not Beneficial for IC with Ulcers

  Lee CL, Kuo HC. Intravesical botulinum toxin a injections do not benefit patients with ulcer type interstitial cystitis. Pain Physician. 2013 Mar;16(2):109-16.
  In a study of treatment outcomes among IC patients with and without ulcers (Hunner’s lesions), researchers in Taiwan found that botulinum toxin A (BoNT-A) offered no benefit to those with ulcers. Ten patients with ulcers and 30 without (all of whom did not respond to conventional treatments) received botox injections to the bladder every six months for two years. Six months after the final botox treatment, patients without ulcers had significant decreases in symptom indexes, problem indexes, visual analog scale pain scores, O’Leary-Sant scores, and frequency of episodes, as well as increased functional bladder capacity. In comparison, patients with ulcers showed no significant change in any clinical or urodynamic variable.
  
  

• GAGs Therapy Improves Bladder Mucosa

  Costantini E, Lazzeri M, Pistolesi D, Del Zingaro M, Frumenzio E, Boni A, Pietropaolo A, Fragalà E, Porena M. Morphological Changes of Bladder Mucosa in Patients Who Underwent Instillation with Combined Sodium Hyaluronic Acid-Chondroitin Sulphate (Ialuril®). Urol Int. 2013 Mar 13. [Epub ahead of print]
  To determine the effect of glycosaminoglycans (GAGs) therapy on the bladder wall, Italian researchers treated 21 women who had either IC or recurrent urinary tract infections (rUTIs) with repeated intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS). They first received four weekly instillations, then two instillations every two weeks, and ended with two monthly instillations. Post-treatment follow-up showed an improvement in bladder mucosa and in symptoms in all but two patients.
  
  

• Oxygen Therapy After DMSO Prolongs Treatment Benefits

  Gallego-Vilar D, García-Fadrique G, Povo-Martin I, Salvador-Marin M, Gallego-Gomez J. Maintenance of the Response to Dimethyl Sulfoxide Treatment Using Hyperbaric Oxygen in Interstitial Cystitis/Painful Bladder Syndrome: A Prospective, Randomized, Comparative Study. Urol Int. 2013 Mar 13. [Epub ahead of print]
  When researchers in Spain followed dimethyl sulfoxide (DMSO) treatment for IC with hyperbaric oxygen (HBO) therapy, they found that the benefits of DMSO were maintained longer. In the first phase of the study, DMSO was given to all 20 patients. In the second phase, 10 of them received HBO. Out of 20 patients, 14 experienced clinical improvement after DMSO in all of the evaluated symptoms (pain, frequency and urgency of voids, nocturia, and quality of life). After the second phase, all patients who received HBO had more substantive improvements that were maintained longer than in the DMSO only group.
  
  

• 12-Week Course of Heparin/Lidocaine Combo Relieves IC Symptoms

  Nomiya A, Naruse T, Niimi A, Nishimatsu H, Kume H, Igawa Y, Homma Y. On- and post-treatment symptom relief by repeated instillations of heparin and alkalized lidocaine in interstitial cystitis. Int J Urol. 2013 Feb 22. doi: 10.1111/iju.12120. [Epub ahead of print]
  Ninety percent of IC patients enrolled in a study of the effects of a 12-week course of heparin and lidocaine reported symptom relief one month after treatment. For this study, 32 patients with refractory IC (unresponsive to traditional treatment) received 12 weekly instillations of 20,000 U heparin, 5mL of 4 percent lidocaine, and 25mL of 7 percent sodium bicarbonate. The treatment was deemed effective (symptoms slightly improved or better on a global response assessment) by 60 percent of patients at week four and 76.7 percent at week 12, and by 90 percent, 46.7 percent, and 16.7 percent of patients at 1, 2, and 6 months after the last treatment. Other assessment measures—such as O'Leary and Sant's symptom index and problem index, visual analog scale for pain, and frequency volume chart variables—also improved significantly by the fourth week of treatment and beyond. Although the benefits gradually decreased once treatment ended, they remained statistically significant for 2 months after that, leading the Japanese researchers to conclude that this combination treatment is safe and effective for IC relief and that further studies should be done to determine the optimal number and interval of instillations.
  
  

• TENS Reduces Pain and Improves QoL in Swiss Men with CPP

  Schneider MP, Tellenbach M, Mordasini L, Thalmann GN, Kessler TM. Refractory chronic pelvic pain syndrome in men: can transcutaneous electrical nerve stimulation help? BJU Int. 2013 Feb 22. doi: 10.1111/bju.12005. [Epub ahead of print]
  After 12 weeks of TENS (transcutaneous electrical nerve stimulation) treatment, 60 Swiss men with refractory chronic pelvic pain syndrome reported improvements in symptoms and quality of life. Researchers used the patients’ pain diaries and their responses to the quality of life item of the NIH Chronic Prostatitis Symptom index to evaluate the effects of the treatment at baseline, after 12 weeks of treatment, and at the last known follow-up. The mean pain visual analog scale decreased significantly after 12 weeks of TENS, from 6.6 at the start of treatment to 3.9 at the end. The men’s qualify of life also improved: before treatment all 60 men felt mostly dissatisfied, unhappy, or terrible, and after treatment 29 of the men (48 percent) felt mostly satisfied, pleased, or delighted. The positive effect lasted for a mean of 43.6 months in 21 of these men.
  
  

• Multiple Treatment with BoNT-A Offers More Relief than Single

  Kuo HC. Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome. Pain Physician. 2013 Jan;16(1):E15-23.
  Researchers in Taiwan conducted a study of single vs. repeated injections of onabotulinum toxin-a (BoNT-A) and found that two, three, or four injections were more effective in decreasing bladder pain and increasing bladder capacity than were single injections. Of the 81 study participants, 20 received single injections, 19 received two injections, 12 had three injections, and 30 had four. The injections were spaced six months apart, and those who had just one served as controls. After repeated treatments (two, three, or four injections) patients had significant improvements in O'Leary-Sant symptom indexes and problem indexes, visual analog pain score, functional bladder capacity, and daytime frequency. The success was greatest for those receiving three or four injections compared to just one, but the long-term success rates were the same for those receiving two, three, or four injections.
  
  

• Pollen Extract Linked to Improved QoL in CP

  Cai T, Luciani LG, Caola I, Mondaini N, Malossini G, Lanzafame P, Mazzoli S, Bartoletti R. Effects of pollen extract in association with vitamins (DEPROX 500®) for pain relief in patients affected by chronic prostatitis/chronic pelvic pain syndrome: results from a pilot study. Urologia. 2013 Jan 16;0(0):0. doi: 10.5301/RU.2013.10597. [Epub ahead of print]
  An Italian study of 20 young men with chronic prostatitis/chronic pelvic pain showed improved quality of life after the men took vitamins containing pollen extract for one month. Once a day for 30 days, they took two tablets of DEPROX 500®, and after one month, 90 percent (18 out of 20) reported less pain and increased quality of life, as measured by NIH-CPSI and IPSS questionnaires.
  
  

• Vulvar Pain Successfully Decreased with Botox, Gabapentin Use

  Jeon Y, Kim Y, Shim B, Yoon H, Park Y, Shim B, Jeong W, Lee D. A retrospective study of the management of vulvodynia. Korean J Urol. 2013 Jan;54(1):48-52. doi: 10.4111/kju.2013.54.1.48. Epub 2013 Jan 18.
  In a retrospective study of botulinum toxin A and gabapentin in the treatment of vulvodynia, Korean researchers found that both treatments successfully reduced chronic vulvar pain. For the study, 62 women with vulvodynia received gabapentin and 11 received botulinum toxin A. The effectiveness of each was measured by visual analogue scale (VAS), which showed a significant decrease in pain after both types of treatment. In the gabapentin group, the VAS score decreased from 8.6 before treatment to 3.2 after treatment; in the botulinum toxin A group, the VAS went from 8.1 to 2.5. Side effects were few and subsided with general antibiotics and nonsteroidal anti-inflammatory drugs.
  
  

• Adolescent IC May Also Require a Multimodal Approach

  Hammett J, Krupski TL, Corbett ST. Adolescent pelvic pain: Interstitial cystitis. J Pediatr Urol. 2013 Feb 11. pii: S1477-5131(13)00019-3. doi: 10.1016/j.jpurol.2013.01.012. [Epub ahead of print]
  The exact prevalence of interstitial cystitis (IC) in children is unknown, but urologists and other healthcare providers are seeing and diagnosing IC in children. There has been little information published about children and IC, therefore treatments specific to children and IC are very limited. Researchers out of the University of Virginia reported a case of a 13-year-old girl with IC who was treated with multiple therapeutic strategies outlined by the American Urological Association IC treatment guidelines. With this multimodal approach, the young patient did have symptom relief. This report shows that therapeutic strategies for adults with IC may also be helpful for adolescent IC.
  
  

• Effects of Hydrodistention Improved with Bladder Training

  Hsieh CH, Chang WC, Huang MC, Su TH, Li YT, Chang ST, Chiang HS. Hydrodistention plus bladder training versus hydrodistention for the treatment of interstitial cystitis. Taiwan J Obstet Gynecol. 2012 Dec;51(4):591-5. doi: 10.1016/j.tjog.2012.11.001.
  Researchers in Taiwan found that IC patients benefited more from hydrodistention (HD) treatment when it was followed by bladder training (BT—learning to urinate on a set schedule). For the study, 70 patients were randomly assigned to one of two groups: HD treatment alone or HD plus BT. Weekly for eight weeks after HD, and then monthly for six months after that, the patients recorded in a diary their urgency, bladder pain, number of daytime and nighttime voids per day, and volume per void. At the 6-month mark, there was a significant decrease in urgency and bladder pain in the HD plus BT group. This group also had greater volume per void and fewer voids throughout the day and night.
  
  

• IC Relief with Repeated Injections of Onabotulinum Toxin A

  Pinto R, Lopes T, Silva J, Silva C, Dinis P, Cruz F. Persistent therapeutic effect of repeated injections of onabotulinum toxin a in refractory bladder pain syndrome/interstitial cystitis. J Urol. 2013 Feb;189(2):548-53. doi: 10.1016/j.juro.2012.09.027. Epub 2012 Dec 14.
  In a Portuguese study of 16 women with refractory IC, repeated injections of onabotulinum toxin A decreased pain and urinary frequency and increased voided volume and patient quality of life for an average of nine months. The women received four consecutive injections of 100 U of onabotulinum toxic A in 10 trigonal sites (10 U per site), with re-treatment allowed three months after each injection. Symptoms were assessed at the first month and every three months after each injection; improvements were similar after each treatment and persisted for 6-12 months.
  
  

• Myofascial PT Deserves Closer Look for Pelvic Pain Treatment

  Fitzgerald MP, Anderson RU, Potts J, Payne CK, Peters KM, Clemens JQ, et al. Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes. J Urol. 2013 Jan;189(1 Suppl):S75-85. doi: 10.1016/j.juro.2012.11.018.
  After a small feasibility study of myofascial physical therapy vs. global therapeutic massage for urological pelvic pain revealed greater benefits from myofascial therapy, researchers recommend a full-scale randomized clinical trial of physical therapy methods. For the feasibility study, 23 men with chronic prostatitis and 24 women with IC were randomized to receive up to 10 weekly, 1-hour treatments of either myofascial PT or global therapeutic massage. The response rate of 57 percent in the myofascial group and 21 percent in the global massage group prompted the recommendation for further study.
  
  

• Physical Therapy Helps Those with Vulvodynia

  Polpeta NC, Giraldo PC, Teatin Juliato CR, Gomes Do Amaral RL, Moreno Linhares I, Romero Leal Passos M. Clinical and therapeutic aspects of vulvodynia: the importance of physical therapy. Minerva Ginecol. 2012 Oct;64(5):437-45.
  Even though vulvodynia affects an estimated 16 percent of women aged 18 to 64 worldwide, much remains unknown about it, including how to treat it effectively. In a bibliographic review of research on vulvodynia pathophysiology and treatment, these researchers found that physical therapy is associated with higher success rates in treatment. The literature review shows that various types of physical therapy improve pelvic floor muscle dysfunction, thereby decreasing symptoms and increasing women’s quality of life.
  
  

• Literature Review Supports Sacral  Neuromodulation for Bladder Pain

  Srivastava D. Efficacy of sacral neuromodulation in treating chronic pain related to painful bladder syndrome/interstitial cystitis in adults. J Anaesthesiol Clin Pharmacol. 2012 Oct;28(4):428-35. doi: 10.4103/0970-9185.101890.
  To determine whether sacral neuromodulation is a safe and effective treatment for the chronic pain of interstitial cystitis, this researcher reviewed published literature using MEDLINE and EMBASE [1950- Nov 2011], the Cochrane Database of Systematic reviews (CDSR), Scopus, CINAHL, BIOSIS, the Cochrane controlled trials register, the science citation index, and TRIP DATABASE. He found that 70.8 percent (170 out of 244) patients had a successful experience at the trial stage. The only randomized controlled trial reported a decrease in Visual analogue pain scores of 49 percent for sacral nerve stimulation and 29 percent for pudendal nerve stimulation at 6-month follow-up. Nine observational studies reported a decrease in pain scores/pain medication use at long term follow-up after permanent sacral neuromodulation. One study showed an 80 percent improvement in Global response assessment score.
  
  

• Study Shows Potential for CAM, Need for Further Research

  Interstitial cystitis patients' use and rating of complementary and alternative medicine therapies. O'Hare PG 3rd, Hoffmann AR, Allen P, Gordon B, Salin L, Whitmore K. Int Urogynecol J. 2012 Nov 14. [Epub ahead of print]
  A study on complementary and alternative medicine (CAM) for the treatment of interstitial cystitis (IC) indicated that slightly more than half of those who tried CAM found it helpful, and that those who did benefit were more likely to have been recently diagnosed. For the study, which was initiated by the Interstitial Cystitis Association in 2009, participants completed an Internet-based survey about whether they received an IC diagnosis and how long ago and whether they tried CAM and who recommended it. They also rated 49 therapies on a 5-point scale. Of those who responded to the survey, 1,982 had been diagnosed with IC. Of that group, 84.2 percent had tried CAM (55 percent upon a doctor’s recommendation). Nearly 83 percent had tried diet or physical therapy and 69 percent had tried other therapies. Patients rated 22 of the therapies positively, 20 negatively, and 7 were inconclusive. Among those rated positively were dietary management and pain management (physical therapy, heat and cold, meditation and relaxation, acupuncture, stress reduction, exercise, and sleep hygiene). The study authors encourage the development of randomized, placebo-controlled studies of various CAM therapies.
  
  

• Repeated BoNT—A Injections Provide Greater Symptom Relief

  Shie JH, Liu HT, Wang YS, Kuo HC. Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome. BJU Int. 2012 Sep 3. doi: 10.1111/j.1464-410X.2012.11466.x. [Epub ahead of print]
  Research has shown that a single set of botulinum toxin A (BoNT-A) injections relieves symptoms of interstitial cystitis (IC), but doesn’t offer long-term relief. This study of 23 women with IC indicates that repeated injections do. Among the 23 women who received the single injection were 11 who got three repeated injections every 6 months. Compared to the women who had only one dose, the ones who had multiple BoNT-A injections had reduced inflammation, lower apoptotic signaling molecules, lower pain scores, and less glomerulation, as well as improvements in results from immunohistochemical staining. The researchers conclude that repeated BoNT-A injections are necessary for greater IC treatment success.
  
  

• Hyaluronic Acid—No Dosage Differences?

  Lai MC, Kuo YC, Kuo HC. Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: A comparative randomized assessment of different regimens. Int J Urol. 2012 Aug 26. doi: 10.1111/j.1442-2042.2012.03135.x. [Epub ahead of print]
  Researchers found that there were no significant differences in the 6-month outcomes of treatment with 40 mg hyaluronic acid whether the instillations were given as 4 weekly plus 5 monthly instillations or every other week for 12 weeks. Thirty IC patients were assigned to each regimen and at the end of treatment, both groups showed significant improvement in symptom scores and Quality of Life Index.
  
  

• More Evidence Needed to Support Antidepressants for Vulvodynia

  Leo RJ, Dewani S. A systematic review of the utility of antidepressant pharmacotherapy in the treatment of vulvodynia pain. J Sex Med. 2012 Sep 13. doi: 10.1111/j.1743-6109.2012.02915.x. [Epub ahead of print]
  Antidepressants are often recommended in the treatment of vulvodynia, but there hasn’t been an evaluation of study results to see if this recommendation is warranted. A medical literature search identified 13 published studies to assess. The researchers found a number of shortcomings in the study designs, including lack of clear inclusion/exclusion criteria, small sample sizes, and lack of comparison groups, among others. Although most of the studies used tricyclic antidepressants (TCAs), evidence supporting the benefits of TCAs was limited, and none of the studies compared the efficacy of different types of antidepressants. The researchers conclude that despite some women with vulvodynia reporting a benefit from using antidepressants, there isn’t sufficient evidence to support recommending it. They encourage additional research to identify specific characteristics of women with vulvodynia who might benefit from antidepressant therapy.
  
  

• Continuous IV Lidocaine Shows Promise for Pain

  Nickel JC, Jain P, Shore N, Anderson J, Giesing D, et. al. Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: safety and efficacy of a new drug delivery device.
  Whether given orally or intravesically, it has been difficult to get a high enough concentration of IC drugs into the bladder to have a good effect. Although previous attempts to use a drug delivery method from within the bladder have been unsuccessful, Canadian researchers recently had good results with a small device that moved freely within the bladder and was well tolerated by both patients and controls. Using this continuous lidocaine-releasing intravesical system (LiRIS), the researchers treated 16 women with IC/BPS with Hunner’s lesions or bladder hemorrhages and a control group of healthy volunteers with either 200mg or 650mg of lidocaine over a course of two weeks. Both doses were well tolerated, and 64 percent of the patients responded to the treatment with improvements in pain, urgency, voiding frequency, and questionnaire responses, as well as healing of Hunner’s lesions in 5 of 6 patients. There was still a 64 percent response rate two weeks later, and pain reduction was maintained for several months after the device was removed.
  
  

• Bladder Capacity Predicts Failure of DMSO Cocktail

  Stav K, Beberashvili I, Lindner A, Leibovici D. Predictors of Response to Intravesical Dimethyl-sulfoxide Cocktail in Patients with Interstitial Cystitis. Urology. 2012 Jul;80(1):61-5.
  Researchers in Tel Aviv found that an anesthetic bladder capacity of less than 675mL predicted treatment failure of a dimethyl-sulfoxide cocktail among IC patients. In this study, 51 patients received a weekly combination of DMSO, hydrocortisone, heparin sulfate, and bupivacaine for 12 weeks. They completed 3-day bladder diaries and visual analog scales for pain, and were evaluated by the researchers every 3 weeks during the study using the O’Leary-Sant questionnaire, then every three months for a year after the study. Response was defined as a 30 percent or greater decrease in questionnaire scores from baseline. Sixty-one percent of the patients responded to treatment, and factors including age, menopausal state, body mass index, diabetes, and cystometric and anesthetic bladder capacities were all associated with treatment response. Small anesthetic bladder capacity was the only independent predictor of treatment failure (odds ratio 83, 95 percent CI, P<.001).
  
  

• Age Doesn’t Affect Success of Neuromodulation

  Peters KM, Killinger KA, Gilleran J, Boura JA. Does patient age impact outcomes of neuromodulation? Neurourol Urodyn. 2012 June 5. [Epub ahead of print]
  To determine whether age affects the success of sacral neuromodulation in patients with refractory voiding symptoms, researchers at the Oakland University William Beaumont School of Medicine conducted a 2-year prospective observational study of the treatment’s outcomes in three patient groups: those under age 40, age 40-64, and 65 and older (328 total patients, 83 percent of which were women). Urge incontinence was predominant in those over 40, while more patients under 40 had IC. For all three groups, urinary frequency, nocturia, incontinence episodes, urgency, and overactive bladder questionnaire scores improved over time. Physical quality of life improved among the 40-64 year olds and mental quality of life improved for the <40 and 40-64 groups. Complications and revisions to the implant differed among the groups (higher among those <40). The researchers conclude that the patient’s age does not affect treatment success, but that continued study is needed.
  
  

• Trigger Point Massage vs. Global Massage for IC Relief

  Fitzgerald MP, Payne CK, Lukacz ES, Yang CC, Peters KM, Chai TC, et al. Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness. J Urol. 2012 Jun;187(6):2113-8. Epub 2012 Apr 12.
  Everyone enjoys a nice massage, but if you’re seeking relief from IC symptoms, this study suggests a trip to the physical therapist may be more helpful than a trip to the spa. Eighty-one women who had had IC for 3 years or less, who had similar symptoms at the start of the study, and who had pelvic floor tenderness upon examination, were randomly assigned to receive either 10 treatments of myofascial physical therapy or global therapeutic massage. In this myofascial physical therapy, also called trigger point release, a physical therapist massages tender points in the pelvic floor muscles. Afterward, both groups reported less pain, urgency, and frequency, as well as a decrease in O’Leary-Sant IC Symptom and Problem Index. However, 59 percent of the group that received the myofascial physical therapy reported moderately to markedly improved symptoms overall, compared to 26 percent of the global therapeutic massage group.
  
  

• Intravesical HA and CS Shows Long-Term Benefit

  Cervigni M, Natale F, Nasta L, Mako A. Intravesical hyaluronic acid and chondroitin sulphate for bladder pain syndrome/interstitial cystitis: long-term treatment results. Int Urogynecol J. 2012 May 9. [Epub ahead of print]
  To determine whether the known short-term benefits of intravesical instillations of hyaluronic acid (HA) and chondroitin sulphate (CS) can be sustained over a long period of time, researchers followed 12 IC patients receiving the treatment for 3 years. These patients, who had not responded to other treatments, were given a combination of 1.6 percent HA and 2 percent CS. The treatment resulted in a sustained improvement in symptoms for the duration of the 3-year study: compared to the patients’ baseline assessments, at the completion of the study the mean number of daily voids had decreased from 17.8 to 11.9, the mean volume per void had increased from 136.8 ml to 180.9 ml, and the patients’ quality of life had improved (based on a visual analogue scale, 3-day voiding diaries, and validated questionnaires).
  
  

• PBS/IC Pain Relief Greater When Hydrodistention is Combined with RTX

  Ham BK, Kim JH, Oh MM, Lee JG, Bae JH. Effects of combination treatment of intravesical resiniferatoxin instillation and hydrodistention in patients with refractory painful bladder syndrome/interstitial cystitis: a pilot study. Int Neurourol J. 2012 March;16(1):41-6. Epub 2012 March 31.
  In a Korean study comparing the effectiveness of hydrodistention treatment with and without intravesical resiniferatoxin (RTX), the combination treatment provided the greatest pain relief. Both treatments resulted in significant improvements in urinary frequency, functional bladder capacity, and pain three months after treatment, but pain relief was significantly higher in those who received hydrodistention with RTX. This randomized prospective study was conducted with 18 patients who had proven PBS/IC that did not respond to traditional treatment. The authors call for larger studies to clarify the effectiveness of this combination therapy.
  
  

• Major Surgery May Help Some—But Not All—with Disabling IC

  Andersen AV, Granlund P, Schultz A, Talseth T, Hedlund H, Frich L. Long-term experience with surgical treatment of selected patients with bladder pain syndrome/interstitial cystitis. Scand J Urol Nephrol. 2012 Mar 27. [Epub ahead of print].
  Norwegian researchers set out to determine whether cystectomy, subtotal cystectomy with bladder augmentation, and urinary diversion with intact bladder are effective surgeries to relieve symptoms in patients with disabling BPS/IC that is not responsive to traditional treatment. They gave questionnaires about postoperative pain and satisfaction to 41 patients who had had one or more of these surgeries at Oslo University Hospital between 1983 and 2004. Thirty-eight patients responded, and among them 74 percent were free of pain and 68 percent were satisfied with the end result. There was no difference in pain between those who had their bladder removed and those who had not. Pain after surgery appears to be linked to symptom duration before surgery: those who had pain for a long time prior to surgery were more likely to have persistent pain afterward.
  
  

• Case Report: Steroid Injection of Tarlov Cysts Relieved IC-Like Pelvic Pain

  Freidenstein J, Aldrete JA, Ness T. Minimally invasive interventional therapy for tarlov cysts causing symptoms of interstitial cystitis. Pain Physician. 2012 Mar;15(2):141-6.
  In this retrospective case study, researchers at the University of Alabama describe a treatment that reduced pelvic pain in two patients who had IC symptoms (bladder pain and urgency) and Tarlov cysts on the sacral nerve roots. Researchers treated the cysts with low volume, targeted caudal epidural steroid injections. The results: both patients had nearly complete pain relief for 6 months to 2 years. These patients are still being followed and continue to report benefit from the treatment. The research team including Dr. Timothy Ness a past pilot program awardee whose research suggested that oxytocin and similar drugs might be useful for the treatment of the pain of interstitial cystitis.
  
  

• Researchers Toast DSMO Cocktail as First-Line IC Therapy

  Hung MJ, Chen YT, Shen PS, Hsu ST, Chen GD, Ho ES. Risk factors that affect the treatment of interstitial cystitis using intravesical therapy with a dimethyl sulfoxide cocktail. Int Urogynecol J. 2012 Mar 17. [Epub ahead of print
  Dimethyl sulfoxide (DMSO) bladder instillation is a standard therapy for IC that has varying degrees of success. When it loses its effectiveness, it’s often combined with other medications in a “cocktail.” Researchers in Taiwan hypothesized that starting newly diagnosed patients with the cocktail, rather than waiting until after using DSMO alone, would give better treatment results. They enrolled 90 women with newly diagnosed IC. Of the 84 who completed treatment (six dropped out due to intolerable bladder irritation), 65.5 percent had a greater than 50 percent improvement in their symptoms, measured by the IC symptom and problem index. Regression analysis showed three variables that reduced the DSMO cocktail’s effectiveness: advanced cystoscopic glomerulations, microscopic hematuria, and urodynamic detrusor underactivity. Otherwise, the authors suggest that DSMO cocktail may be considered first-line therapy for IC.
  
  

• New Vulvodynia Research Needed

  Itza F, Zarza D, Gomez-Sancha F, Salinas J, Bautrant E. Update on the diagnosis and treatment of vulvodynia. Actas Urol Esp. 2012 Feb 23. [Epub ahead of print]
  In a 10-year review of medical literature on vulvodynia, Spanish researchers conclude that despite some advances, we need new research and more regulated studies. They conducted a Medline/PubMed and Cochrane Library search using the terms vulvodynia, vestibulodynia, etiology, epidemiology, diagnosis, neurophysiological test, and treatment or management. Their critical analysis revealed few control or placebo-controlled groups or double-blind studies in research; that the scales, indexes and questionnaires used to evaluate pain before and after treatment are not uniform; that the diagnostic criteria used is debatable; and that neurophysiological diagnostic resources are underused. Although most medical treatments in these studies were not effective, surgery (vestibulectomy) did show effectiveness, and physiotherapy and cognitive behavioral therapy look promising.
  
  

• NY Times Says “Cocktail of Popular Drugs May Cloud Brain”

  Fox C, Richardson K, Maidment ID, Savva GM, Matthews FE, Smithard D, Coulton S, Katona C, Boustani MA, Brayne C. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011 Aug. [Epub 2011 Jun 24].
  This study looked at the impact of anticholingeric medicines on cognitive functioning among a group of individuals 65 years of age and older. Researchers concluded that after adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance, seniors who took drugs with anticholinergic (aCH) effects had a greater degree of cognitive impairment. Highlighted in the February 27, 2012 Health section of the New York Times (“Cocktail of Popular Drugs May Cloud Brain”), this study caught our eye because some of the drugs mentioned are used for treatment of IC. Though the scienctific rigor of the study is soft, an awareness of the long-term use of aCH medicines among IC patients is important because many people with IC are on multiple medicines with cumulative aCH effects. What can you do about it? Keep a written record of the medicines and over-the-counter products that you take and review these with your IC healthcare team. Also, ask your family and friends to let you know if they notice personality or memory changes—these may indicate the need to rethink your IC treatment protocol. And, talk with your healthcare team about non-medication treatment options to incorporate into your treatment plan such as physical therapy, stress management, massage, stretching, dietary changes, healthy sleeping habits, and other lifestyle changes.
  
  

• Know Your Trigger Foods to Help Manage IC

  Friedlander JI, Shorter B, Moldwin RM. Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions. BJU Int. 2012 Jan.11. doi: 10/1111/j.1464-410X.2011.10860.x.[Epub ahead of print]
  A review of data from questionnaire-based studies shows that about 90 percent of people with IC/BPS are sensitive to certain foods. Common culprits that tend to increase symptoms are citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic drinks, and spicy foods. Not everyone surveyed reacted to the same foods or in the same ways, possibly because some people had additional chronic pain conditions (irritable bowel syndrome, chronic fatigue, fibromyalgia, neuropathic pain, vulvodynia, and headache). Figuring out which foods increase symptoms, through an elimination diet, for example, could be an important part of managing IC.
  
  

• Shocking Treatment for CP/CPP

  Zeng XY, Liang C, Ye ZQ. Extracorporeal shock wave treatment for non-inflammatory chronic pelvic pain syndrome: a prospective, randomized and sham-controlled study. Chin Med J (Engl). 2012 Jan;125(1):114-8.
  A Chinese study of shock treatments for pelvic pain in men with non-inflammatory chronic prostatitis/chronic pelvic pain syndrome resulted in decreased pain and improved quality of life. The men were randomly assigned to receive either extracorporeal (on the outside of the body) shock wave treatment (ESWT) of 20,000 shock wave impulses in 10 sessions over a two-week period, or a sham procedure. Using the National Institutes of Health Chronic Prostatitis Symptom Index, the researchers scored each group on pain and urinary symptoms and their effect on quality of life at five points during the study: before treatment, mid-treatment, at the end point, and at 4- and 12-weeks after treatment. The total symptom index score of the ESWT group was significantly lower after treatment than before, and their scores for pain and quality of life issues also decreased. In contrast, there were no significant decreases in symptom index score or pain domain after treatment among the sham group.
  
  

• Marijuana Could Allow Lower Opioid Doses for Chronic Pain

  Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011 Dec;90(6):844-51. doi: 10.1038/clpt.2011.188. Epub 2011 Nov 2.
  Chronic pain patients who were already taking long-acting opioid medications got extra relief when they inhaled vaporized marijuana. That implies that using medical marijuana could allow chronic pain patients to use less opioid medication. The study included 21 chronic pain patients who took twice-daily doses of sustained-release morphine or oxycodone. They stayed in the hospital for 5 days, where they inhaled vaporized cannabis the first evening, three times a day on the second through the fourth day, and again on the morning of the fifth. From the first through the fifth day, their blood was sampled every 12 hours. Blood tests showed there was no change in the levels or activity of the opioids, but the patients had significant reductions in pain, averaging 27 percent. The University of California press release on this study quoted Donald Abrams, MD, saying, “What we need to do now is look at pain as the primary end point of a larger trial. Particularly, I would be interested in looking at the effect of different strains of cannabis.” Dr. Abrams was quoted in the ICA Update’s story on medical marijuana for IC in the Fall 2011 issue. Strains do seem to make a difference, as you can see in the comments of IC patients and caregivers quoted in that story, supporting Dr. Abrams call for studies of different strains.
  
  

• Vaginal Diazepam Helps Just Where it Hurts

  Carrico DJ, Peters KM. Vaginal diazepam use with urogenital pain/pelvic floor dysfunction: serum diazepam levels and efficacy data. Urol Nurs. 2011 Sep-Oct;31(5):279-84, 299.
  Many IC patients know that intravaginal diazepam (Valium) can be very helpful for pelvic floor dysfunction and urogenital pain, but we didn’t know whether the drug could stay in your system and cause problems down the road. Now, this study shows that the diazepam either doesn’t get absorbed or, if it does, doesn’t stick around very long. These researchers treated 21 women for pelvic floor muscle pain with daily diazepam. One month after treatment, 62 percent of the patients said they were moderately or markedly improved and their vulvar pain scores decreased. In addition, their pain scores were lower during a pelvic exam. Blood tests at that time showed that diazepam levels were normal.
  
  

• Review of Urinary Tract Botox Offers Hope—with Caution

  Yokoyama T, Chancellor MB, Oguma K, Yamamoto Y, Suzuki T, Kumon H, Nagai A. Botulinum toxin type A for the treatment of lower urinary tract disorders. Int J Urol. 2012 Jan 6. doi: 10.1111/j.1442-2042.2011.02946.x. [Epub ahead of print]
  This review of botulinum toxin A (Botox) for bladder and prostate conditions notes that it can have positive effects on IC, refractory idiopathic detrusor overactivity, neurogenic detrusor overactivity, and benign prostatic hyperplasia. Because FDA approved it for treating urinary incontinence caused by nerve-related bladder muscle overactivity (as in spinal cord injury or multiple sclerosis), Botox will become more widely used and urologists will become more familiar with how to use it. “However,” wrote the authors, “further robust evidence should be awaited.”
  
  

• Elmiron May Help by Reducing Inflammation

  Sunaga T, Oh N, Hosoya K, Takagi S, Okumura M. Inhibitory Effects of Pentosan Polysulfate Sodium on MAP-Kinase Pathway and NF-κB Nuclear Translocation in Canine Chondrocytes In Vitro. J Vet Med Sci. 2011 Dec 28. [Epub ahead of print]
  This laboratory research indicates that pentosan polysulfate (Elmiron) may reduce the inflammatory process in cells that is induced by the cytokine IL-1beta. The research helps describe the biochemical pathway for this. With an eye to treatment of osteoarthritis, the investigators used dog chondrocytes, the cells that make up cartilage, but the anti-inflammatory effect might also be at work in IC bladder cells.
  
  

• Preop Test, GABA Drugs May Show Whether Neuromodulation Will Work

  Martellucci J, Naldini G, Carriero A. Sacral nerve modulation in the treatment of chronic pelvic pain. Int J Colorectal Dis. 2011 Dec 29. [Epub ahead of print]
  From 2004 to 2009 at this hospital in Italy, 27 patients (including 2 men) underwent preoperative tests for sacral nerve modulation for pelvic pain. Of those, 16 had neuromodulators implanted. Mean pain scores dropped from approximately 8 to 2 six months later and remained at about that level at follow-ups as long as five years later. (The mean follow-up was 37 months). The authors noted that a positive preoperative screening test as well as a positive response to gabapentin (Neurontin) or pregabalin (Lyrica) predicted success for pain. Having pain in more than one location and having pain after stapler surgery seemed to be negatives for success. (The abstract did not specify what types of pelvic pain were treated.)
  
  

• Special Fabric Eases Vulvar Woes

  D’Antuono A, Bellavista S, Negosanti F, Zauli S, Baldi E, Patrizi A. Dermasilk briefs in vulvar lichen sclerosus: an adjuvant tool. J Low Genit Tract Dis. 2011 Oct;15(4):287-91. doi: 10.1097/LGT.0b013e31821380a0.
  Women with a vulvar skin problem who wear underwear made with a specialty fabric seem to get better and faster improvement with treatment than women who wear cotton underwear. The fabric, called DermaSilk, is a knitted medical grade silk that has been stripped of its outer coating and bonded with a type of antimicrobial shield. It has been shown to be useful for patients with allergic skin problems, eczema, and vulvovaginal yeast. This study tested use of the DermaSilk underwear in women with vulvar lichen sclerosis—itchy and irritated white patches on the vulva. The women wore either the specialty or cotton briefs while they were undergoing treatment with a topical steroid and vitamin E moisturizer. When they were examined at one and six months of treatment, the women wearing the specialty briefs showed significantly greater improvement in symptoms of burning, skin irritation, pain, and redness than the women who wore cotton briefs, and their itching improved faster as well.
  
  

• Alkalinized Lidocaine Plus Heparin Gives Immediate Relief

  Parsons CL, Zupkas P, Proctor J, Koziol J, Franklin A, Giesing D, Davis E, Lakin CM, Kahn BS, Garner WJ. Alkalinized Lidocaine and Heparin Provide Immediate Relief of Pain and Urgency in Patients with Interstitial Cystitis. J Sex Med. 2011 Nov 14. doi: 10.1111/j.1743-6109.2011.02542.x. [Epub ahead of print]
  In this multicenter controlled study, IC patients got immediate relief of pain lasting at least 12 hours after an instillation of alkalinized lidocaine plus heparin. This prospective, double-blind, crossover study with 18 patients aimed to confirm a previous uncontrolled study of this treatment. In this study, each patient received instillations with the drug and with a control solution in random order, and neither the patients nor the researchers knew which was which. After instillation of the drug, the average reduction in pain 12 hours later was 42 percent, whereas the average reduction for patients getting the control instillation was 21 percent. Patients who got the drug rated their overall symptoms as having lessened by 50 percent, whereas the patients who got the control instillation said their overall symptoms 13 percent better. Note that some IC clinicians think heparin may interfere with lidocaine, so they administer these two separately.
  
  

• Instillation Effective after Other Therapies Fail

  Matsuo T, Shida Y, Hayashida Y, Sakai H. Intravesical therapy of heparin and lidocaine for interstitial cystitis : a case report. [Article in Japanese] Hinyokika Kiyo. 2011 Sep;57(9):513-6.
  This report describes the case of a 64-year-old woman with IC who got relief from instillations of heparin and alkalinized lidocaine after other treatments didn’t help her. (She had undergone treatment with hydrodistention, a tricyclic antidepressant, an overactive bladder drug, suplatast tosilate, and kampo extracts, which are traditional Japanese herbal medicines). She got two instillations a week for 12 months with 20,000 units of heparin, 200 mg of lidocaine, and 7 percent sodium bicarbonate. Her O’Leary-Sant IC symptom index score improved from 20 to 8 and her IC problem index score from 16 to 8. Her bladder capacity increased from 90 mL to 300 mL.
  
  

• Chronic Pain Often Accounts for Marijuana Use

  Zvolensky MJ, Cougle JR, Bonn-Miller MO, Norberg MM, Johnson K, Kosiba J, Asmundson GJ. Chronic pain and marijuana use among a nationally representative sample of adults. Am J Addict. 2011 Nov-Dec;20(6):538-42. doi: 10.1111/j.1521-0391.2011.00176.x. Epub 2011 Oct 4.
  Analysis of a national survey including 5,672 US adults showed that marijuana users are often people in chronic pain. After the researchers controlled for sociodemographic factors, depression, and alcohol abuse or dependence, they found that there was a significant relationship between chronic pain and marijuana use. Many users of marijuana at present or who had ever used it had chronic pain during their lifetime. In addition, people who had chronic pain at the time of the survey were likely to have used marijuana at some time. On the other hand, there was no significant relationship between having chronic pain at the time of the survey and being a current user of marijuana, but that might have been a statistical problem, noted the authors. Although they noted that people in chronic pain may be using marijuana as a “maladaptive coping strategy,” it may also be that people in chronic pain may be getting needed relief from marijuana and that they may be using it to ease pain rather than for recreation. Another explanation for the last finding might be that people who use marijuana for chronic pain may not be using it today because their pain is being managed successfully with other pain treatments.

  
  Like other chronic pain patients, some IC patients have been using marijuana to ease their pain and other symptoms. And others in states where medical marijuana is legal, or soon may be, want to know whether medical marijuana could help. Read the Fall 2011 issue of the ICA Update to learn what we know so far about marijuana's effects on IC, what IC patients have to say, and what the risks and benefits may be.

• Can Psychological Therapy Ease Pelvic Pain? We Still Don’t Know

  Champaneria R, Daniels JP, Raza A, Pattison HM, Khan KS. Psychological therapies for chronic pelvic pain: systematic review of randomized controlled trials. Acta Obstet Gynecol Scand. 2011 Nov 4. doi: 10.1111/j.1600-0412.2011.01314.x. [Epub ahead of print]
  Does the literature show that psychological therapy improves outcomes of pelvic pain treatment? No, concluded these researchers who combed the literature for randomized, controlled trials of psychological therapies in women with chronic pelvic pain compared with standard gynecological treatment or another form of psychological therapy. Only four of the 107 articles they identified with potential satisfied their analytic criteria But in these four studies, the change in pain scores with psychological therapy were not longstanding or reliable enough to draw conclusions about whether the therapy helped.
  
  

• Randomized Studies Needed for GAG Layer Replacers

  Damiano R, Cicione A. The role of sodium hyaluronate and sodium chondroitin sulphate in the management of bladder disease. Ther Adv Urol. 2011 Oct;3(5):223-32.
  Using hyaluronic acid or chondroitin sulfate has definitely shown decreased rates of urinary tract infections. But the results for IC with either or both of these glycosaminoglycan layer replacers are less clear. Between 2002 and 2011, nine studies on the use of these instillations for IC were published, two of them in combination with hydrodistention. Those two were the only studies controlled in any way. The lack of controlled, randomized studies has hampered interpretation of the evidence. Controlled studies large enough to produce conclusive results are needed.
  
  

• Liposomes Look Promising for IC

  Lee WC, Chuang YC, Lee WC, Chiang PH. Safety and dose flexibility clinical evaluation of intravesical liposome in patients with interstitial cystitis or painful bladder syndrome. Kaohsiung J Med Sci. 2011 Oct;27(10):437-40. Epub 2011 Jul 23.
  This small, open-label study of liposome instillation in IC patients showed promising results. We reported on these results when the study was presented at the American Urological Association’s annual meeting in 2010, and now the results have been published in a journal. Of the 17 patients in the study, 12 got liposome instillations once a week for four weeks, and five got instillations twice a week for four weeks. The instillations were well tolerated, and the incidence of adverse effects was low. O’Leary-Sant Symptom and Problem Index scores improved significantly with both treatments, but the improvement was greater with the twice-a-week regimen. The authors called for large-scale, placebo-controlled studies to assess the treatments’ effectiveness.
  
  

• Encouraging Results in Small Study of Tibial Stimulation

  Gaj F, Andreuccetti J, Speziali F, Trecca A, Crispino P. Chronic pelvic pain treatment with posterior tibial nerve stimulation. [Article in Italian] Clin Ter. 2011 Jul-Aug;162(4):e111-e114.
  This comparison of two different regimens of Percutaneous Tibial Nerve Stimulation (PTNS) showed “complete recovery” in a third to nearly half of 35 patients with chronic pelvic pain. (It was unclear whether any of the patients had IC.) In the group of 17 patients who underwent 12 PTNS stimulation sessions once a week, treatment was a success for 11 (63 percent), and 4 (36 percent) recovered completely. Of the 18 patients who underwent 12 PTNS sessions three times a week, treatment was a success for 12 (67 percent), and 5 (45 percent) recovered completely. PTNS shows encouraging results in pelvic pain patients who are not responding to standard pain therapy, concluded the authors.
  
  

• Evidence Needs to Grow Stronger for Botulinum Toxin

  Jabbari B, Machado D. Treatment of Refractory Pain with Botulinum Toxins-An Evidence-Based Review. Pain Med. 2011 Sep 29. doi: 10.1111/j.1526-4637.2011.01245.x. [Epub ahead of print]
  This review looked at the evidence in the medical literature for using botulinum toxin to treat pain. Although the therapy is supported very well with high-quality studies for some conditions, such as cervical dystonia and chronic migraine, the evidence for pelvic pain is still at “level C,” meaning “possibly effective.”
  
  

• Mexican Clinic Uses DMSO, Elmiron

  Flores-Carreras O, Martínez-Espinoza CJ, González-Ruiz MI. Experience in the treatment of interstitial cystitis: review of 17 cases. [Article in Spanish] Ginecol Obstet Mex. 2011 Mar;79(3):125-30.
  The authors at a clinic in Jalisco, Mexico, reported on their experience using DMSO instillation and pentosan polysulfate (Elmiron) to treat 17 patients. Eighty-two percent of the patients had significant improvement in symptoms and quality of life. (Mean scores on the IC Symptom Index went from an average of 17 to 4.5, and scores on the IC Problem Index from 14.8 to 4.1.)
  
  

• Sex, Cycle Make a Difference in Opioid Response

  Liu NJ, Chakrabarti S, Schnell S, Wessendorf M, Gintzler AR. Spinal Synthesis of Estrogen and Concomitant Signaling by Membrane Estrogen Receptors Regulate Spinal {kappa}- and {micro}-Opioid Receptor Heterodimerization and Female-Specific Spinal Morphine Antinociception. J Neurosci. 2011 Aug 17;31(33):11836-45.

  Different types of opioids work differently in men and women, and now we know why. This team of researchers found that the types of opioid receptor interact differently in males and females. The research showed that female laboratory rats have nearly five time more of a complex of the mu and kappa opioid receptors in their spinal cords than males do. In addition, those levels in females are four times higher when both estrogen and progesterone are at their peak than when the hormone levels are low. That means that some opioids might be effective for pain when the hormone levels are high but also that some opioids may even heighten pain levels when hormones levels are low. You and your doctors may need to consider the stage of your menstrual cycle before you decide which drugs to take when. Also, the difference may be critical for managing pain in postmenopausal and elderly women.

• Meta-Analysis Shows No Big IC Winner

  Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ. Contemporary Management of the Painful Bladder: A Systematic Review. Eur Urol. 2011 Sep 9. [Epub ahead of print]
  Cyclosporine and amitriptyline were the only treatments that showed a consistently great effect on IC in randomized trials, showed this meta-analysis. It pooled data from studies published between 1990 and 2010, covering 7,709 adult patients. The nonrandomized trials showed that the most frequently adopted treatment is oral pentosan polysulfate (Elmiron) and that the use of onabotulinumtoxinA injected into the bladder is increasing. But this wasn’t really saying a lot, since the authors considered the evidence limited for the few treatments we do have.

• Physical Therapy May Be Crucial for Resolving Pelvic Pain

  Díaz-Mohedo E, Barón-López FJ, Pineda-Galán C. Etiological, Diagnostic and Therapeutic Consideration of the Myofascial Component in Chronic Pelvic Pain. Actas Urol Esp. 2011 Sep 12. [Epub ahead of print]
  Myofacial alterations are common with IC and other conditions that cause chronic pelvic pain. The myofascial problems may be responsible for perpetuating the symptoms. Plus, treatment may not be able to resolve symptoms unless the myofascial pain is treated specifically. Those were the conclusions of these physiotherapists from their systematic review of the medical literature from 2000 to 2009.

• Hyaluronic Acid-Chondroitin Sulfate Instillation Looks Helpful

  Porru D, Leva F, Parmigiani A, Barletta D, Choussos D, Gardella B, Daccò MD, Nappi RE, Allegri M, Tinelli C, Bianchi CM, Spinillo A, Rovereto B. Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis. Int Urogynecol J. 2011 Sep 9. [Epub ahead of print]
  An uncontrolled study of instillations of hyaluronic acid and chondroitin sulfate improved symptoms significantly on multiple measures. The 22 IC patients in this study got instillations of 40 mL of sodium hyaluronic acid 1.6 percent and chondroitin sulfate 2.0 percent in 0.9 percent saline solution once a week for 8 weeks, then once every 2 weeks for the next 6 months. Patients’ urgency scores went down from an average of 6.5 to 3.6, their pain scores from 5.6 to 3.2, and their daily frequency from 14 to 11. Their urine volume increased from an average of 129.7 mL to 162 mL. In addition, the patients’ scores on the IC Symptom and Problem Index improved from an average of 25.7 to 20.3 and Pain Urgency Frequency scores from 18.7 to 12.8.

• Allergy Drug Helps Older Male Patient

  Traut JL, Macdonald ES, Spangler ML, Saxena S. Montelukast for symptom control of interstitial cystitis. Ann Pharmacother. 2011 Sep;45(9):e49. Epub 2011 Aug 23.
  This report describes the case of a 64-year-old man with IC who got relief with montelukast (Singulair) when other drugs didn’t help, including solifenacin (Vesicare), dutasteride (Avodart, a 5-alpha reductase inhibitor prescribed for an enlarged prostate), and tamsulosin (Flomax, an alpha blocker prescribed for urinary symptoms with an enlarged prostate). He started taking montelukast 10 mg/day for allergy, and when he did, he had substantial improvement in urinary urgency and pain. The improvement disappeared when montelukast was stopped.

• “Stop Hurting” Antibody Discovery Could Bring New Approach to Pain

  Dawes JM, Calvo M, Perkins JR, Paterson KJ, Kiesewetter H, Hobbs C, Kaan TKY, Orengo C, Bennett DLH, McMahon SB. CXCL5 Mediates UVB Irradiation–Induced Pain. Sci Transl Med. 2011;3(90):90ra60.
  Researchers at King’s College London have found a molecule in the body that controls sensitivity to pain, a previously unknown chemokine called CXCL5. Chemokines are immune signaling proteins that play a role in inflammation, often recruiting immune cells to injured tissue. The researchers found CXCL5 by inducing persistent abnormal sensitivity to pain through ultraviolet B (UVB) irradiation—that is, sunburn—in humans and rats. They measured more than 90 inflammatory mediators in the skin, with CXCL5 being induced the most in human skin. CXCL5 resulted in similar hypersensitivity in rats’ skin with the typical recruitment of the immune cells neutrophils and macrophages. The researchers then used a neutralizing antibody targeting CXCL5, which significantly reduced the sensitivity to pain.

  “This study isn’t just about sunburn–we hope that we have identified a potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis,” said Prof Steve McMahon, from the Wolfson Centre for Age-Related Diseases at King’s and head of the London Pain Consortium in a King’s College press release. Dr David Bennett, Wellcome clinical scientist at King’s and honorary consultant neurologist at King’s College Hospital, added, “‘We intend to extend this approach to other types of pain and in particular to study patients suffering from chronic pain with the hope that this will speed up the process of turning science into effective treatments for patients.” The approach may lead to an entirely new class of pain drugs useful for chronic pain. Read more about the discovery and watch a video of Prof McMahon explaining the research here: http://www.kcl.ac.uk/newsevents/news/newsrecords/2011/07July/Discovery-why-sunburn-hurts-could-lead-new-pain-relief-drugs-inflammatory-conditions.aspx

• New Neurostimulation Technique Eases Chronic, Intractable Pain

  Verrills P, Vivian D, Mitchell B, Barnard A. Peripheral Nerve Field Stimulation for Chronic Pain: 100 Cases and Review of the Literature. Pain Med. 2011 Aug 3. doi: 10.1111/j.1526-4637.2011.01201.x. [Epub ahead of print]
  Peripheral nerve field stimulation is a new type of neurostimulation that involves placing stimulating electrodes in the painful areas themselves and not in or on the nerve or spinal cord, making the technique less invasive. These pain specialists looked at the results in 100 patients who got the stimulators for various types of chronic pain, including pelvic and groin pain. Patients’ started with an average pain score of 7.4 and got a mean pain reduction of 4.2 on an 11-point scale. At an average of 8 months after the procedure, 72 percent of patients had cut down their use of pain medication. The reduction in disability was significant among the patients who got the treatment for low back pain. There were no long-term complications. The authors said the technique has the potential to fundamentally change the way we think about pain management.

• New Mast Cell Target May Produce IC Treatments

  Park CS, Bochner BS. Potential targeting of Siglecs, mast cell inhibitory receptors, in interstitial cystitis. Int Neurourol J. 2011 Jun;15(2):61-3. Epub 2011 Jun 30.
  Eliminating mast cells or blocking their function could be key to treating IC pain and inflammation. The sialic-acid-binding immunoglobulin-like lectins (Siglecs) were first identified 30 years ago as markers of leukemia and lymphoma 30 years ago and have become known as important inhibitory regulators of immune-cell signaling. Siglec-8, identified in 2009, has been discovered to be expressed in mast cells. There, it inhibits degranulation—the process of the mast cell spilling its contents and causing symptoms. When Siglec-8 is engaged on eosinophils, which are important mediators of allergic responses, these cells die. In this review, the authors propose that targeting Siglecs such as this one on mast cells could lead to IC treatments.

• Heart Healthy is Urinary Tract Healthy

  Moyad MA. Heart health = urologic health and heart unhealthy = urologic unhealthy: rapid review of lifestyle changes and dietary supplements. Urol Clin North Am. 2011 Aug;38(3):359-67.
  What lifestyle changes and dietary supplements help urologic conditions? Urologist Mark Moyad, MD, says that the heart-healthiest recommendations have consistently served as the safest and most potentially effective options in urology for benign prostatic hyperplasia, chronic nonbacterial prostatitis, interstitial cystitis, multiple urologic cancers, male infertility, male and female sexual dysfunction, kidney stones, and Peyronie disease.

• Evidence Level Low But Results Good for Hyperbaric Oxygen

  Gallego Villar D, García Fadrique G, Povo Martín IJ, Miralles Aguado J, Garau Perelló C, Sanchis Verdú L, Gimeno Argente V, Bosquet Sanz M, Rodrigo Aliaga M, Claramonte Ramón FJ, Gallego Gómez J. Hyperbaric oxygen treatment in urology. Arch Esp Urol. 2011 Jul;64(6):507-516.
  This article in a Spanish urology journal reviews the literature on the use of hyperbaric oxygen therapy (HBO) in urologic disorders, including IC. The 56 published papers were mostly case reports, so the level of evidence is low. Nevertheless, the results were good or very good, so, the authors said, it seems that HBO can be very useful in urological diseases related to low oxygen in the tissues.

• Amphetamines, Alternatives for Pelvic Pain

  Check JH, Cohen R. Chronic pelvic pain—traditional and novel therapies: part II medical therapy. Clin Exp Obstet Gynecol. 2011;38(2):113-8.
  These gynecologists have been using sympathomimetic amines such as dextroamphetamine sulfate to treat some cases of IC and other types of pelvic pain based on the theory that defects in the sympathetic nervous system cause pelvic pain. The more conventional therapies to use that fit in with this theory that have the most benefit and least risk, they said, are oral contraceptives, low dosage progesterone/progestins, and low-dose impeded androgens, which are androgens with a minimal masculinizing effect. Danazol (Danocrine) is an example. The authors believe that dextroamphetamine sulfate may be the most effective therapy with the fewest side effects, but it is a schedule II drug that has not been approved for pelvic pain and must be used off label. In the same issue of this journal, these authors also report on using dextroamphetamine sulfate for backache in a woman who was assumed to have herniated lumbar discs. Within hours the pain diminished. She was pain free within a week, and the relief persisted for months.

• Simpler Technique for the Last-resort Treatment

  Rowley MW, Clemens JQ, Latini JM, Cameron AP. Simple Cystectomy: Outcomes of a New Operative Technique. Urology. 2011 Aug 1. [Epub ahead of print]
  The urologists describe a simple technique for cystectomy. Among the 23 patients who underwent the procedure between 2007 and 2010 at the University of Michigan Health System, five of the patients had interstitial cystitis that couldn’t be helped by other treatments. Cystectomy is the absolute last-resort treatment for IC. The technique can be performed quickly with minimal blood loss and complications.

• Group Calls for Multidisciplinary Approach to Management

  Nickel JC, Tripp D, Gordon A, Pontari M, Shoskes D, Peters KM, Doggweiler R, Baranowski AP. Update on urologic pelvic pain syndromes: highlights from the 2010 international chronic pelvic pain symposium and workshop, August 29, 2010, Kingston, Ontario, Canada. Rev Urol. 2011;13(1):39-49.
  This group of urologists plus a pain doctor and nurse put together their recommendations on how to manage the urologic chronic pelvic pain conditions IC and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The authors emphasize that IC and CP/CPPS patients need a multidisciplinary and multimodal pain management approach.

• Botulinums Not Interchangeable

  Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, Gravas S, Madersbacher S. Contemporary Management of Lower Urinary Tract Disease With Botulinum Toxin A: A Systematic Review of Botox (OnabotulinumtoxinA) and Dysport (AbobotulinumtoxinA). Eur Urol. 2011 Jul 13. [Epub ahead of print]
  Two types of botulium toxin A have been studied for various types of lower urinary tract dysfunction, including IC. There are two commonly used preparations onabotulinumtoxinA (Botox) and abobotulinumtoxinA (Dysport). These authors systematically reviewed the medical literature on outcomes with these two preparations and found that there is high-level evidence for the use of onabotulinumtoxinA and abobotulinumtoxinA in adults with neurogenic detrusor overactivity (such as in spinal cord injured patients), but only for abobotulinumtoxinA in children with neurogenic detrusor overactivity (such as in children with spina bifida). Only onabotulinumtoxinA has level 1 evidence supporting its use in IC. That does not imply, wrote the authors, that onabotulinumtoxinA is more effective than abobotulinumtoxinA. Nevertheless, they said the two preparations should not be used interchangeably.

• Hypnosis May Ease Pelvic Pain Symptoms

  Rodney U Anderson, Thomas F Nagy, Elaine K Orenberg, Angie Morey, Patricia Glowe. Feasibility Trial of Medical Hypnosis and Cognitive Behavioral Therapy for Men With Refractory Chronic Prostatitis/Chronic Pelvic Pain Syndrome. UroToday Int J. 2011 Aug;4(4):art46. doi:10.3834/uij.1944-5784.2011.08.02.
  Hypnosis seems to help men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). That’s a good indicator that it may help people with IC as well. (See our article on hypnosis and IC in the Spring 2011 issue of the ICA Update.) This is the first study we know of on hypnosis in pelvic pain. However, hypnosis wasn’t used in this study as the sole mind-based treatment; it was combined with cognitive behavioral therapy and guided imagery. But that combination is probably typical for pain patients who undergo hypnotherapy because well-qualified practitioners are often trained psychologists or psychiatrists. Sixteen men who had had pain for a median of seven years and who had high pain scores underwent seven weekly sessions in which they learned to hypnotize themselves. The researchers looked at changes in their symptoms and whether the patients followed through with their home exercises, using audiotapes of their sessions and behavioral therapy workbooks. Six months later, the median score on the NIH Chronic Prostatitis Symptom Index (CPSI) went down by a median of 10.5 points in 57 percent of the patients. (The abstract did not note what the change was for the other 43 percent.) The pain and quality-of-life CPSI subscores improved significantly. McGill pain scores decreased by a median of 6.5 points. Most patients (88%) said that continued self-hypnosis was effective for relieving symptoms and coping.

  
  Buy the Spring 2011 issue of the ICA Update with the article “Hip to Hypnosis for IC: A Conversation with Jan Burte, PhD.”

  Learn about medical hypnosis at the Stanford Center for Integrative Medicine, where this research was done: http://stanfordhospital.org/clinicsmedServices/clinics/complementaryMedicine/hypnosis.html

  Listen and watch to webcasts of David Spiegel, MD, one of Stanford’s hypnosis staff and director of the Center on Stress and Health here: http://stresshealthcenter.stanford.edu/

• New Approach Helps Drugs Stick Around in Your Bladder

  Barthelmes J, Perera G, Hombach J, Dünnhaupt S, Bernkop-Schnürch A. Development of a mucoadhesive nanoparticulate drug delivery system for a targeted drug release in the bladder. Int J Pharm. 2011 Jun 24. [Epub ahead of print]
  This preliminary test of a new approach to getting drugs to stick around in the bladder got one to stay stuck on the bladder lining 14 times better than a comparison substance (unmodified chitosan nanoparticles). The nanoparticle drug carriers are based on chitosan, a biopolymer derived from chitin. (In nature, chitin helps form the external armor of insects and crustaceans, such as lobsters.) This biopolymer-drug combination adds a new approach to targeted drug delivery systems for the bladder, such as liposomes and hydrogels.
  
  

  Read more about exciting new approaches to delivering drugs to the bladder: http://www.pharmatutor.org/articles/novel-targeted-drug-delivery-systems-new-age-weapons-for-bladder-diseases?page=0,1

• Lots of Success, But Lots of Revisions, with Sacral Nerve Stimulation

  Norderval S, Rydningen M, Lindsetmo RO, Lein D, Vonen B. Sacral nerve stimulation. Tidsskr Nor Laegeforen. 2011 Jun 17;131(12):1190-1193.
  These Norwegian clinicians discussed the uses of sacral nerve stimulation and noted that the implanted stimulator give a sustainable effect in 50 to 90 percent of chronic pelvic pain patients who respond during the test period. But up to 76 percent of patients will need repeated follow-up visits, including pacemaker reprogramming or reoperations because of diminished effectiveness. The stimulators last for 3 to 10 years and must be replaced when the battery has been depleted. Replacement requires reoperation. Most patients need close follow-up to get the best results, the authors emphasized.
  
  

• Pain Control Effects Not Clear for Sacral Neuromodulation

  Marcelissen T, Jacobs R, van Kerrebroeck P, de Wachter S. Sacral neuromodulation as a treatment for chronic pelvic pain. J Urol. 2011 Aug;186(2):387-93. Epub 2011 Jun 17.
  Sacral neuromodulation has shown its worth for urinary symptoms, but for pelvic pain, the answer isn’t clear, concluded these authors who reviewed the literature. They identified a total of 12 articles that addressed the issue, 10 of which were mainly about IC. Of those 10, 7 reported outcomes, showing mean reductions in pain scores of 40 to 72 percent. The reoperation rate with long-term follow-up ranged between 27 and 50 percent. The success rates after implantation ranged from 60 to 77 percent. That’s not enough to say what the role of sacral neuromodulation should be in treating chronic pelvic pain, said the authors, who recommended larger prospective trials with long-term follow-up.
  
  

• Testing Stimulator Leads During Implant Surgery May Not Be Needed

  Peters KM, Killinger KA, Boura JA. Is sensory testing during lead placement crucial for achieving positive outcomes after sacral neuromodulation? Neurourol Urodyn. 2011 Jun 14. doi: 10.1002/nau.21122. [Epub ahead of print]
  Testing leads when a sacral neuromodulator is implanted has the drawback of putting patients under lighter anesthesia than usual. But that may not be necessary, concluded these urologists. They looked at the records of their experience with implantation and found that testing during implantation surgery didn’t necessarily improve the implantation rates or clinical outcomes. Of their 141 patients who had sacral neuromodulator implants, 86 (61 percent) had had sensory testing during their operation and 55 (39 percent) had not. There was no real difference in implant rates (90 percent and 87 percent, respectively) between the groups. There was also no significant difference between the groups in terms of symptom improvement. Thirteen percent (11 out of 16 patients) who had the sensory testing had the implant removed, compared with only 5.5 percent (3 out of 55 patients) in the group that didn’t have the testing, but the difference was not statistically significant.
  
  

• Companies Target Vanilloid Channels for Pain Drug Development

  Eid SR. Therapeutic Targeting of TRP Channels - The TR(i)P to Pain Relief. Curr Top Med Chem. 2011 Jun 14. [Epub ahead of print]
  The so-called “hot pepper” or vanilloid receptor 1 (TRPV1) has been the focus of a lot of pain and IC research, but there are more TRP channels. Small biotech and pharmaceutical companies are working on developing small molecules that target these channels, too, which include TRPV3, TRPV4, TRPA1, and TRPM3. All this drug development activity reflects the potential importance of these drug targets in inflammatory and neuropathic pain, urinary incontinence, IC, and even in types of prostate cancer, said the authors.
  
  

• Treatment Improves Sexual Function, Quality of Life

  Schmid C, Berger K, Müller M, Silke J, Mueller MD, Kuhn A. Painful bladder syndrome: management and effect on sexual function and quality of life. Ginekol Pol. 2011 Feb;82(2):96-101.
  These Swiss gynecologists treated 69 patients with IC with tetracycline (not considered standard treatment in the United States) and bladder instillations with anesthetic –containing cocktails or DMSO. Treatment improved quality of life and sexual function as well as pain, nighttime urination, frequency, and urgency.
  
  

• Internal Massage Tool Allows At-Home Treatment

  Anderson R, Wise D, Sawyer T, Nathanson BH. Safety and Effectiveness of an Internal Pelvic Myofascial Trigger Point Wand for Urologic Chronic Pelvic Pain Syndrome. Clin J Pain. 2011 May 25. [Epub ahead of print]
  Many IC patients know that regular pelvic trigger point massage can really take down symptoms. But it’s not always practical or affordable to go to physical therapy frequently to get it. It’s helpful to be able to massage the trigger points on your own, and a massaging tool can help patients do that, something that many physical therapists are already recommending to IC patients. Now, there’s study evidence that this approach is helpful. These investigators, including the authors of A Headache in the Pelvis, have tested a “wand” that also includes a pressure-measuring device and found it to be safe and effective in the 106 men and 7 women who used it. The patients were carefully trained how to use the instrument and then used it themselves at home several times a week for six months. At the start of the study, the patients’ median sensitivity on a 10-point scale was 7.5. After six months, the score decreased significantly to a 4. Most (about 96 percent) patients said the wand was either very effective or moderately effective in alleviating pain. No serious adverse events occurred.
  
  

• Hyperbaric Oxygen May Offer Long-term Relief

  Tanaka T, Nitta Y, Morimoto K, Nishikawa N, Nishihara C, Tamada S, Kawashima H, Nakatani T. Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan. BMC Urol. 2011 May 24;11(1):11. [Epub ahead of print]
  In this uncontrolled study from Japan, 7 out of 11 IC patients who weren’t helped by other treatments got relief with hyperbaric oxygen. For some, significant improvement lasted for more than two years. The patients, seen between 2004 and 2009, were treated for 60 minutes a day, five days a week, for two or four weeks. Their average pain scores on the PUF scale went from 7.7 down to 3.5, and the urgency score from 6.6 to 4.3. Frequency and scores on the interstitial cystitis symptom index also showed a sustained and significant decrease. Two patients who got an additional course of treatment about a year after the first one “have not suffered impairment” for more than two years. Side effects were minimal, with one case of a temporary eustachian tube problem and three cases of middle ear inflammation that went away. The authors called hyperbaric oxygen a “potent” treatment for IC that doesn’t respond to conventional therapy. You can read this article free at http://www.biomedcentral.com/1471-2490/11/11

• Purinergic Receptors Are Ripe Target for Bladder Drugs

  Sun Y, Chai TC. Role of Purinergic Signaling in Voiding Dysfunction. Curr Bladder Dysfunct Rep. 2010 Aug 26;5(4):219-224.
  The physiologic signals transmitted when ATP binds to purinergic receptors, such as P2X and P2Y, may play a role in many bladder disorders, including IC, neurogenic bladder resulting from spinal cord injury, lower urinary tract symptoms, diabetes, and aging. This signaling goes on in central and peripheral nerves, bladder muscle, and bladder lining. Drugs that target these receptors hold promise for treating bladder disorders, said the authors.
  
  

• Drugs Targeting Purinergic Receptors Hold Promise for IC

  Burnstock G, Kennedy C. P2X Receptors in Health and Disease. Adv Pharmacol. 2011;61:333-72.
  This review article highlights the potential for treatments aimed at the P2X receptor, which ATP latches onto. These receptors occur on both central and peripheral nerves and also on many other types of cells. Changes in the expression of these receptors have been found in a number of conditions, and these receptors have been found to play a role in IC bladder pain. A number of drugs aimed at these receptors—both blockers and stimulators—are being researched in many disorders, including chronic neuropathic and inflammatory pain, depression, cystic fibrosis, dry eye, irritable bowel syndrome, IC, dysfunctional urinary bladder, and cancer.
  
  

• Canadian Chiropractors “Moderately Open” to Pelvic Pain Treatment

  Parkinson J, Lau J, Kalirah S, Gleberzon BJ. Attitudes of clinicians at the Canadian Memorial Chiropractic College towards the chiropractic management of non-musculoskeletal conditions. J Can Chiropr Assoc. 2011 Jun;55(2):107-19.
  This survey of the faculty of a chiropractic college showed that the 22 chiropractors were “moderately open” to treating some nonmusculoskeletal conditions. They were most positive about the potential of treating constipation, chronic pelvic pain, painful periods asthma, infant colic, and vertigo with chiropractic techniques. You can read this article free at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095585/?tool=pubmed

• How You “See” Pelvic Pain Could Be Treatment Target

  Berna C, Vincent K, Moore J, Tracey I, Goodwin GM, Holmes EA. Presence of Mental Imagery Associated with Chronic Pelvic Pain: A Pilot Study. Pain Med. 2011 Jun 13. doi: 10.1111/j.1526-4637.2011.01152.x. [Epub ahead of print]
  These mental health professionals asked patients who had prolonged pelvic pain and distress whether they had thoughts about their pain in the form of mental images—and all of them did. Some of the patients also reported that they used mental images to cope. Imagery could provide a good target for pain treatment with behavioral therapy, the authors concluded.
  
  

• AUA Publishes IC Clinical Guidelines

  Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM. AUA Guideline for the Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol. 2011 Apr 15. [Epub ahead of print]
  The American Urological Association finalized its first clinical guidelines for IC, and now, they are published in the association’s journal. You can read the guidelines themselves at http://www.auanet.org (click “Policies, Guidelines & Quality” and then “Guidelines”) and read our summary of the guidelines and guide to what they mean for you in the Spring 2011 issue of the ICA Update.
  
  

• Different Sacral Neuromodulator Strokes for Different Folks

  Marcelissen TA, Leong RK, Nieman FH, de Bie RA, van Kerrebroeck PE, de Wachter SG. The effect of pulse rate changes on the clinical outcome of sacral neuromodulation. J Urol. 2011 May;185(5):1781-5. Epub 2011 Mar 21.
  There’s no ideal pulse rate for a sacral neuromodulator (such as InterStim) for everyone, but adjustments can make a difference for individuals, shows this study. The researchers tried four different pulse rates for six days each in 50 patients who had stimulators for bladder symptoms but were not getting an optimal response. There were no significant differences between the pulse rates in terms of clinical outcomes or voiding, and none of the pulse rates had a clear relationship with pain from the stimulation itself. Nevertheless, individuals got improvement in symptoms and reductions in stimulator pain with changes in the pulse rates. It takes an individual approach to get the best results with stimulators, concluded the investigators.
  
  

• Long-term Elmiron Users Show Better Outcomes

  Al-Zahrani AA, Gajewski JB. Long-term efficacy and tolerability of pentosan polysulphate sodium in the treatment of bladder pain syndrome. Can Urol Assoc J. 2011 Apr;5(2):113-8.
  In taking a retrospective look at 271 IC patients at their institution who took pentosan polysulfate (Elmiron), these urologists saw greater improvement in those who took the drug for more than a year than in those who took it less than a year. Outcomes were also better in patients taking the drug who had severe glomerulations. About half the patients who took pentosan polysulfate had at least 50 percent improvement in their condition. A third of patients decided to stop taking the drug, most often because of poor outcomes. Outcomes were poorer in patients who had nighttime urination (nocturia), overactive bladder muscles, or were smokers.
  
  

• Tarlov Cysts: Overlooked, Undertreated Sources of Pelvic Pain

  Murphy KJ, Nussbaum DA, Schnupp S, Long D. Tarlov cysts: an overlooked clinical problem. Semin Musculoskelet Radiol. 2011 Apr;15(2):163-7. Epub 2011 Apr 15.
  Tarlov cysts, which can cause chronic pelvic and leg pain, are underdiagnosed and very treatable, say these radiologists and clinicians. These cysts are abnormal, fluid-filled sacs at nerve roots—most commonly at the sacral nerve roots S2 and S3. (S3 is where sacral neuromodulator leads are normally placed because this is the major root for nerves that control bladder function.) Older methods to treat these cysts, including open surgery or withdrawing fluids through a needle under imaging guidance, have been risky and not reliably effective. For this reason, many doctors thought that no treatment could be offered or that the cysts didn’t really cause symptoms. Patients, the authors pointed out, were often treated dismissively by doctors who think the cysts don’t cause symptoms or that the pain must be caused by something else. On the other hand, these authors said they have treated more than 100 patients successfully by withdrawing fluids under imaging guidance and then injecting fibrin into the cyst. The results have been excellent with no meaningful complications and no cases of aseptic meningitis, they said. The team concluded that this is a safe, highly effective, first-line treatment for Tarlov cysts that cause symptoms.
  
  

• Potent APF Blockers May Stop IC

  Keay S, Kaczmarek P, Zhang CO, Koch K, Szekely Z, Barchi JJ Jr, Michejda C. Normalization of Proliferation and Tight Junction Formation in Bladder Epithelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome by D-Proline and D-Pipecolic Acid Derivatives of Antiproliferative Factor. Chem Biol Drug Des. 2011 Feb 26. doi: 10.1111/j.1747-0285.2011.01108.x. [Epub ahead of print]
  If you’ve been following the research about antiproliferative factor (APF), you know that this peptide prompts bladder lining damage. Now, the Maryland research team has found some APF derivatives that are potent blockers of APF and could become IC treatments. Specifically, what APF does is decrease the ability of bladder lining cells to proliferate and the cells’ ability to stick together tightly, allowing fluids to get through between cells (making the lining “leaky”). The research team screened APF derivatives for the ability to block antiproliferative activity and normalize the “leakiness” and found two that they said have potential for treatment.
  
  

• Prostaglandin Blocker May Ease Bladder Pain

  Miki T, Matsunami M, Nakamura S, Okada H, Matsuya H, Kawabata A. ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. Pain. 2011 Mar 9. [Epub ahead of print]
  A new type of drug that blocks the receptor for a prostaglandin may be a new approach for treating IC-type bladder pain. Prostaglandins, members of a family of signaling molecules called “prostanoids,” play many roles in the body, including contraction and relaxation of smooth muscles and sensitizing spinal neurons to pain. Nonsteroidal anti-inflammatory drugs work against pain by inhibiting COX enzymes, which interfere with prostaglandin production. ONO-8130, however, blocks one of the prostaglandin receptors (E1). Researchers gave this drug to mice (introducing it into the body cavity) before their bladders were irritated and found it prevented bladder-like pain behavior and referred pain sensitivity. The degree of pain blocking depended on the dose. Putting the particular prostaglandin (E2) blocked by the drug into the bladder prompted a molecular process involved in inflammation and central sensitization, and ONO-8130 blocked that. The researchers said this finding suggests that prostaglandin E2 and its receptor, which ONO-8130 blocks, play a role in processing cystitis-related bladder pain and that this compound and its relatives may be useful for treating bladder pain, especially in IC.
  
  

• Cystistat Eases Symptoms in Small Study

  Figueiredo AB, Palma P, Riccetto C, Herrmann V, Dambros M, Capmartin R. Clinical and urodynamic experience with intravesical hyaluronic acid in painful bladder syndrome associated with interstitial cystitis. Actas Urol Esp. 2011 Mar;35(3):184-187. Epub 2011 Jan 3.
  This before-and-after look at 18 women with IC who got eight weekly sodium hyaluronate (Cystistat) instillations showed their Pelvic Pain Urgency/Frequency (PUF) scores and urodynamics results improved significantly. No toxicity or adverse events were noted. The study comes from Brazil, one of the countries where Cystistat is approved for marketing. It is not approved in the United States because study results did not show enough difference between patients and controls. The authors called for clinical studies that more profoundly evaluate the drug’s therapeutic potential.
  
  

• Cystistat Helps Certain IC Patients

  Van Agt S, Gobet F, Sibert L, Leroi AM, Grise P. Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients. [Article in French] Prog Urol. 2011 Mar;21(3):218-225.
  In a series of 31 IC patients treated with hyaluronic acid (Cystistat) in France, 14 patients (45 percent) had a good response, 2 (7 percent) a partial response, 7 (22 percent) a poor response, and 8 (26 percent) no response. The urologists also performed cystoscopy and biopsy of the bladder, finding that 60 percent of patients who had abnormal looking bladders and bladder tissue got a good or partial response compared with 52 percent overall, so the investigators concluded that the results can be improved by selecting the right patients for the treatment, particularly using cystoscopy and biopsy. France is one of the countries where Cystistat is approved for marketing. It is not approved in the United States because study results did not show enough difference between patients and controls.
  
  

• How IC Patients Fare in Long Haul with Interstim

  Al-Zahrani AA, Elzayat EA, Gajewski JB. Long-term outcome and surgical interventions after sacral neuromodulation implant for lower urinary tract symptoms: 14-year experience at 1 center. J Urol. 2011 Mar;185(3):981-6. Epub 2011 Jan 19.
  In this artice, urologists at Dalhousie University in Halifax, Nova Scotia, took a look at their 14 years of experience with InterStim sacral neuromodulation. Patients were followed up for an average of somewhat more than four years. IC was the reason for implantation in 46 of their 96 (48 percent) patients. Among all their patients, about one-fifth had the devices removed at an average of about a year and a half. The reasons for taking them out were poor results, painful stimulation, and radiation of stimulation to the leg. The success rate was the lowest in IC patients—73 percent—compared with 88 percent in patients with idiopathic urinary retention and 85 percent in patients with urgency urinary incontinence. Overall, 39 percent of their patients needed some kind of revision of the implant. The most common reason for revision was loss of stimulation (in 58 percent of these cases). The introduction of the tined lead dropped the revision rate from 50 percent to 31 percent. Eight patients had the battery changed, and the mean battery life was about eight and a half years.
  
  

• Combination Drug Therapy May Be Helpful

  Lee JW, Han DY, Jeong HJ. Bladder pain syndrome treated with triple therapy with gabapentin, amitriptyline, and a nonsteroidal anti-inflammatory drug. Int Neurourol J. 2010 Dec;14(4):256-60. Epub 2010 Dec 31.
  With a combination of gabapentin (Neurontin), amitriptyline, and nonsteroidal anti-inflammatory drugs, IC patients 38 patients—11 men and 27 women—saw improvement. Before therapy and at one, three, and six months after treatment, the patients completed O’Leary-Sant Symptom and Problem Index questionnaires and a visual analog scale (the abstract did not specify whether this was only for pain or for symptoms in general). One month later, O’Leary-Sant symptom scores improved from an average 11.7 to 4.4 and problem scores from 10.5 to 3.7, while visual analog scale scores improved from 6.7 to 1.8. Further improvements after one month were not statistically significant. Whether this combination is truly helpful needs to be evaluated with a controlled, randomized study.
  
  

• Valid Sham Study Shows Acupuncture Helps Pelvic Pain

  Lee SW, Liong ML, Yuen KH, Leong WS, Khan NK, Krieger JN. Validation of a sham acupuncture procedure in a randomised, controlled clinical trial of chronic pelvic pain treatment. Acupunct Med. 2011 Jan 18. [Epub ahead of print]
  It’s challenging to do a controlled study of acupuncture, but this study achieved it in men with chronic prostatitis/chronic pelvic pain syndrome by using a sham acupuncture unlike the common one. Usually, needles are pressed against the skin and don’t actually puncture it, but this study used needles that do go into the skin, although not very far. The needles were placed a a centimeter away from the true acupuncture point. In this controlled, randomized, double-blind trial, 89 men got either sham acupuncture or the real thing for 10 weeks. Of the 45 patients who got sham treatment, 35 (78 percent) thought they got the real thing, compared with 27 (61 percent) of the 44 patients who got true acupuncture. Thirty-two (73 percent) of the acupuncture patients showed a response, compared with 27 (47 percent) of the sham acupuncture patients—a significant difference. Among the men who also gave blood samples for analysis, levels of beta-endorphin and leucine-enkephalin—natural opioids the body produces—were significantly higher in the acupuncture group.
  
  

• Meditation Changes Brain for Better

  Hölzel BK, Carmody J, Vangel M, Congleton C, Yerramsetti SM, Gard T, Lazar SW. Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Res. 2011 Jan 30;191(1):36-43. Epub 2010 Nov 10.
  Meditation actually changes the brain’s concentration of gray matter, found these researchers. The increases were in areas of the brain associated with learning memory, sense of self, emotional regulation, empathy, and stress. Although meditation is known to improve psychological well being and symptoms of a number of disorders, little has been known about the actual neurologic changes until now. The investigators looked at magnetic resonance (MR) images of the brains of 16 study subjects before and after they participated in a widely used mindfulness training program, called Mindfulness-Based Stress Reduction, for eight weeks. The subjects’ brain images were also compared with images from a group of 17 controls. Analysis of the images confirmed increases in gray matter in the left hippocampus, posterior cingulate cortex, temporoparietal junction, and the cerebellum.
  
  

• New Applications for Sacral Nerve Stimulation

  Dudding TC. Future indications for sacral nerve stimulation. Colorectal Dis. 2011 Mar;13 Suppl 2:23-8.
  Sacral nerve stimulation has been used for bladder symptoms in IC patients and other patients with bladder problems. But now, the techniques are being researched for bowel and sexual dysfunction and the pain that results from them as well as for dysfunction caused by nerve injury and degenerative disease. There’s not much high-quality evidence so far to support these novel uses, said the author. Good-quality, prospective, crossover studies are needed, as is more research into patient selection, surgical technique, and stimulation parameters.
  
  

• Bladder-based Treatments on Hot List for Development

  Kaufman J, Tyagi V, Anthony M, Chancellor MB, Tyagi P. State of the art in intravesical therapy for lower urinary tract symptoms. Rev Urol. 2010 Fall;12(4):e181-9.
  New ways to deliver drugs in the bladder, coat its surface, and even change its genetics show exciting promise. One of the newest approaches with potential for IC is the use of liposomes. These tiny fat bubbles may be able to coat the bladder to prevent irritation and even reduce inflammation. They may also be able to carry helpful medication or even gene-silencing molecules that could turn off nerve growth factor there instead of throughout the body, which has brought problematic side effects, or turn off growth factors that contribute to inflammation. Other new ways to deliver drugs include electromotive drug administration, which uses mild electric current to drive helpful drugs into the tissue, and new microdevices and polymer gels that could keep helpful medicine in the bladder for a long time.
  
  

• Neuromodulation May Affect Bowel Function

  Killinger KA, Kangas JR, Wolfert C, Boura JA, Peters KM. Secondary changes in bowel function after successful treatment of voiding symptoms with neuromodulation. Neurourol Urodyn. 2011 Jan;30(1):133-7. doi: 10.1002/nau.20975. Epub 2010 Oct 6.
  Patients who get neurostimulators for urinary problems can have bowel function changes, too—some positive and some negative. These researchers took a look at the records of patients who got stimulators and who also had bowel problems, such as constipation and/or diarrhea, irritable bowel syndrome (IBS), and fecal incontinence. The patients included 74 with urgency/frequency, 43 with IC, and 11 with urinary retention. For patients who had fecal incontinence, the problem increased over time, reaching a statistically significant difference a year after implantation. On the other hand, the patients who had IBS reported consistently improved bowel function throughout the study period.
  
  

• Trial Fails, But Treatment Door Still Open

  Yang CC, Burks DA, Propert KJ, Mayer RD, Peters KM, Nickel JC, Payne CK, Fitzgerald MP, Hanno PM, Chai TC, Kreder KJ, Lukacz ES, Foster HE, Cen L, Landis JR, Kusek JW, Nyberg LM; Interstitial Cystitis Collaborative Research Network. Early Termination of a Trial of Mycophenolate Mofetil for Treatment of Interstitial Cystitis/Painful Bladder Syndrome: Lessons Learned. J Urol. 2011 Jan 14. [Epub ahead of print]
  In this article, the researchers on a failed trial of an immunosuppressive drug for IC explain why that happened and consider the pros and cons of pursuing this kind of treatment for IC. Aware of the success of Finnish studies of cyclosporine, the Interstitial Cystitis Collaborative Research Network (ICCRN) wanted to do a larger trial here, but couldn’t get placebo pills made for that drug. So, they selected another immunosuppressive drug, mycophenolate mofetil (CellCept), which had shown promise in men with chronic prostatitis/chronic pelvic pain syndrome. But with only 58 patients enrolled in the trial, FDA issued a new safety warning about the drug, and the trial was stopped, although none of the patients showed the worrisome side effects. At that time, the drug looked no better than placebo, but it was too difficult to draw firm conclusions. The questions about the role of autoimmunity in IC and the usefulness of immunosuppressive drugs are still hanging. Studies of bladder tissue have not turned up any consistent relationship between autoimmune complexes and IC. Nevertheless, cyclosporine is helpful. Cyclosporine and mycophenolate mofetil work somewhat differently on immune system T-cells, and they have immune and nonimmune effects that aren’t completely understood. If IC does have an immune basis, it may not be related to T cells. For these reasons, the door is still open for immunosuppression trials in IC, concluded the authors.
  
  

• Blocks Beside the Spine Get Closer Look for Pain

  Richardson J, Lönnqvist PA, Naja Z. Bilateral thoracic paravertebral block: potential and practice. Br J Anaesth. 2011 Feb;106(2):164-71.
  An option for chronic pain is an old anesthesia technique that’s getting new interest—paravertebral block. For this type of nerve block, injections are done on either side of the spine, near where the nerve roots emerge, rather than into the spine. Formerly used as an alternative anesthesia technique, paravertebral block is increasingly being used as a treatment for acute and chronic pain. These authors reviewed the studies on bilateral paravertebral blocks—that is, blocks administered on both sides of the spine rather than just one. It has been used successfully in the thoracic, abdominal, and pelvic areas. Even though the technique requires relatively large doses of local anesthetics, the authors said they have not seen reports of systemic toxicity and that the incidence of complications, such as low blood pressure and collapsed lung, is low. The anesthesiologists called for more studies on the bilateral technique.
  
  

• Botox Called Key Future Treatment Option for Urinary Disorders

  Mangera A, Chapple CR. Use of botulinum toxin in the treatment of lower urinary tract disorders. Current status. Arch Esp Urol. 2010 Dec;63(10):829-41.
  These two urology researchers are enthusiastic about the role of botulinum toxin (Botox and others) for treating lower urinary tract disorders. They said the list of applications is growing, including IC, and that treatments are minimally invasive, “remarkably effective,” and long lasting. A lot of research needs to be done to understand how it works, and better placebo-controlled, randomized trials need to be done to answer the many remaining questions about it.
  
  

• Cyclosporine Successfully Treats IC in Sjögren’s Syndrome Patient

  Emmungil H, Kalfa M, Zihni FY, Karabulut G, Keser G, Sen S, Aksu K. Interstitial cystitis: a rare manifestation of primary Sjögren’s syndrome, successfully treated with low dose cyclosporine. Rheumatol Int. 2011 Jan 22. [Epub ahead of print]
  Just a few case reports in the medical literature show an association with Sjögren’s syndrome and IC, and one of those notes successful treatment with cyclosporine. This one adds to that number. The report comes from Turkey, where a patient with primary Sjögren’s syndrome had chronic IC based on her symptoms and cystoscopy. At first, she received a corticosteroid and the immunosuppressant azathioprine (Imuran) as well as instillations, but these treatments were not effective. Then, she got cyclosporine at a low dose of 1.5 mg/kg/day. After 4 months of cyclosporine, her IC improved and her bladder inflammation had gone down. Even low doses of cyclosporine may be beneficial for treating chronic IC associated in patients with primary Sjögren’s syndrome, said the authors.
  
  

• Hyperbaric Oxygen May Be Helpful

  Passavanti G. Can Hyperbaric Oxygen Therapy (HOT) have a place in the treatment of some urological diseases. Urologia. 2010 Oct-Dec;77(4):257-62.
  These Italian urologists have used hyperbaric oxygen therapy for a number of urologic conditions, including bladder problems, such as urgency-frequency syndrome (a diagnosis sometimes applied to IC patients) and radiation-induced cystitis. The patients with urgency-frequency syndrome had their symptoms and pain go down temporarily. The tool is promising, but it needs further research, said the authors.
  
  

• Botox Applications Reviewed for Finnish Physicians

  Vaarala M, Perttilä I, Hellström P. Botulinum toxin useful in urological problems. [Article in Finnish] Duodecim. 2010;126(21):2511-7.
  This article for Finnish doctors takes a look at botulinum toxin (Botox and others) for overactive bladder, painful bladder, chronic pelvic pain syndromes, and problems with bladder emptying. There are no approved urologic uses, however. The authors said that, in general, treatment is well tolerated and adverse events are predictable and limited to the urogenital tract, but they added that rare severe and fatal complications have been reported.
  
  

• Sacral Neuromodulation Called Promising

  Fariello JY, Whitmore K. Sacral neuromodulation stimulation for IC/PBS, chronic pelvic pain, and sexual dysfunction. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Dec;21(12):1553-8.
  Sacral neuromodulation shows promise for IC, chronic pelvic pain, and sexual dysfunction in pilot studies. Larger, multicenter trials with long-term follow-up are needed, however, to show whether it is truly effective for these conditions. The authors based those conclusions on their review of the studies in the medical literature on the use of sacral neuromodulation for IC, chronic pelvic pain, vulvar vestibulitis, and erectile dysfunction.
  
  

• Sacral Neuromodulation Therapy Evolves

  Thompson JH, Sutherland SE, Siegel SW. Sacral neuromodulation: Therapy evolution. Indian J Urol. 2010 Jul;26(3):379-84.
  This article in an Indian urology journal reviews the developments in sacral neuromodulation for urologists there. The instruments and implantation surgery have changed with introduction of a tined lead, smaller implantable pulse generators and more accurate placement with fluoroscopic imaging. The indications are also expanding beyond overactive bladder and urinary retention to IC, chronic pelvic pain, neurogenic bladder, fecal incontinence, constipation, and dysfunctional elimination syndrome in children.
  
  

• Topical NSAIDs Do a Good Job on Pain

  Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD007402.
  This Cochrane Database systematic review of topical NSAIDs concludes that these medications can provide good levels of pain relief for acute musculoskeletal pain, such as sports injuries, without the adverse effects of the oral forms of medication. The studies reviewed include research on a broad range of NSAIDs in gel, spray, or cream forms, and most studies compared the medication with placebo. The analysts concluded that topical diclofenac, ibuprofen, ketoprofen, and piroxicam had similar effectiveness. On the other hand, indomethacin and benzydamine did not produce results that were significantly better than placebo. Adverse reactions, either local or systemic, were few. There weren’t enough data to reliably compare the medications with each other or with the same oral form of the medication. Although this review focused only on acute pain, it does imply that topical NSAIDs may be useful for other types of pain, which some IC clinicians and their patients are finding.
  
  

• Anesthetic/Steroid Injections Ease Sexual Pain

  Doumouchtsis SK, Boama V, Gorti M, Tosson S, Fynes MM. Prospective evaluation of combined local bupivacaine and steroid injections for the management of chronic vaginal and perineal pain. Arch Gynecol Obstet. 2010 Nov 16. [Epub ahead of print]
  Although this study was not of women with IC, it did show the value of local injections for chronic vaginal and perineal pain—a step forward in bringing this type treatment into wider clinical use. This study focused on women who had chronic vaginal or perineal pain as a result of childbirth or vaginal surgery. The 53 women in the study had one or more injections of a combination of 0.5 percent bupivacaine (10 mL), hydrocortisone (100 mg) and hyaluronidase (1,500 IU). They were followed up ever four weeks, and received additional injections as needed. All the women had pain with intercourse. Most of the women (59) needed two injections; 15 needed one. Pain scores dropped significantly from an average of 6 to 4 after the first injection, and sexual function scores improved significantly from 18 to 29 four weeks after injection. In 69 percent of the 27 sexually active women, pain with intercourse resolved, and 69 percent of the 26 sexually inactive women were able to resume satisfactory sexual activity eight weeks after injection.
  
  

• Studies Point to Diet, Antioxidants as Pelvic Pain Therapy

  Sesti F, Capozzolo T, Pietropolli A, Collalti M, Bollea MR, Piccione E. Dietary therapy: a new strategy for management of chronic pelvic pain. Nutr Res Rev. 2010 Oct 25:1-8. [Epub ahead of print]
  After combing through the medical literature, these gynecologists concluded that diet and antioxidants may be useful therapy for chronic pelvic pain. They looked for studies mentioning chronic pelvic pain and oxidative stress, antioxidants, or dietary therapy. Their focus is somewhat different from an IC diet approach—avoiding flare-producing foods. Instead, they concluded that agents with antioxidant activity can improve chronic pelvic pain without the side effects and metabolic changes of hormonal suppression, a major therapy for endometriosis. Randomized trials with more patients and long-term follow-up are needed to confirm the ideas. Interestingly, patients who answered the ICA’s 2009 Complementary and Alternative Medicine survey identified some antioxidant supplements as helpful.
  
  

• Neuromodulation Results Favor Tined Lead, Staged Implant

  Vaarala MH, Tammela TL, Perttilä I, Luukkonen P, Hellström P. Sacral neuromodulation in urological indications: The Finnish experience. Scand J Urol Nephrol. 2010 Oct 21. [Epub ahead of print]
  This look back at a group of sacral neuromodulation patients in Finland favors the staged implant and tined lead for sacral neuromodulation with InterStim. The patients, who had various types of voiding dysfunction, were followed up for an average of 41 months and for as long as about 12 years. Of the 180 patients who underwent test stimulation, 74 got permanent implants. The time in the operating room was significantly shorter with the tined lead than with the open electrode, which is why the authors favor it. Outcomes were also seemed to be better in patients who underwent a staged implant compared with the one-stage operation with a tined lead device, said the authors. One-fifth of the patients needed a surgical revision.
  
  

• Speed Controls Cold-induced Hives

  Check JH, Cohen R, Check D. Idiopathic edema, a condition associated with pelvic pain and other symptoms in women, as a remedial cause of chronic cold induced urticaria. Clin Exp Obstet Gynecol. 2010;37(3):235-6.
  These gynecologists previously had an article published about dextroamphetamine sulfate (Dexedrine or “speed”) to treat IC in women who have unexplained swelling (idiopathic orthostatic edema). Now, they have tried this drug for cold-induced hives in women with this condition. In these women, the hives didn’t respond to antihistamines but did to the dextroamphetamine. Hives seem to occur at a higher rate in people with IC than in others, but we don’t know whether cold-induced hives are more common.
  
  

• Look for All Causes is Key to Pelvic Pain Treatment Success

  Benjamin-Pratt AR, Howard FM. Management of chronic pelvic pain. Minerva Ginecol. 2010 Oct;62(5):447-65.
  To treat chronic pelvic pain (CPP) well, find all the sources of the pain, these gynecologists urge. Pelvic pain is a common complaint for women in gynecology and primary care, and doctors need to look, not only for obstetric and gynecologic sources of pain, but also at possible gastrointestinal, neurologic, musculoskeletal, and urologic disorders. The authors emphasized the importance of doing a detailed physical exam. Gynecologic causes of pain include endometriosis, pelvic inflammatory disease, adhesive disease, pelvic congestion syndrome, ovarian retention syndrome, ovarian remnant syndrome, adenomyosis, and leiomyomas. Some nongynecologic causes include IC, irritable bowel syndrome, pelvic floor tension myalgia, and abdominal myofascial pain syndrome. The treatments can be directed at the specific causes or toward general pain management, but using both approaches at once may be the most effective, said the authors.
  
  

• Getting Over the IC Drug Development Impasse

  Wyllie MG. Interstitial cystitis: a negative ongoing situation? BJU Int. 2010 Nov;106(9):1401-2.
  The author of this editorial was a leader of the study of an alkalinized lidocaine preparation and delivery system (PD 597) that was presented at the American Urological Association meeting in 2008. Although enthusiasm was high for this treatment, little has happened with it since. In this editorial, Dr. Wyllie offers his ideas about why this and other drugs haven’t been developed for IC. He pointed out that pentosan polysulfate (Elmiron) was approved without the kinds of studies now called for by the International Conference on Harmonization guidelines—two double-blind, placebo-controlled studies with at least 100 patients taking the drug for a year, which suggests that other drugs for IC shouldn’t require studies this extensive either. Nevertheless, this high bar is there, and doing studies this extensive is difficult because a disease-based definition is lacking, and the potential financial return is not seen to be high. The approval process for orphan drugs would be easier, but there are too many IC patients for drugs to fit that definition. “We are nearing the end of the last chapter in the development of new drugs for IC if we are to follow a conventional route for regulatory approval,” Dr. Wyllie wrote. That’s a problem, since he sees evidence from patient advocacy groups and message boards that there’s still a great need for effective therapy and that there’s a fair amount of dissatisfaction with pentosan polysulfate. What’s more, pentosan polysulfate can be obtained in Europe only on a “named patient” basis, similar to getting an investigational drug in the United States. Several hyaluronic acid and chondroitin instillations, which are glycosaminoglycan (GAG) layer enhancers, are available (with variable support for their effectiveness) as “devices.” Dr. Wyllie suggests that these already accepted GAG treatments combined with PD 597 might be a valuable strategy for getting more effective therapy to IC patients, similar to the way combination strategies that have become accepted for prostate enlargement.
  
  

• Migraine/epilepsy Drug May Help with Ejaculatory Pain

  Calabrò RS, Marra A, Quattrini F, Gervasi G, Levita A, Bramanti P. Central Neuropathic Pain: An Unusual Case of Painful Ejaculation Responding to Topiramate. J Sex Med. 2010 May 26. [Epub ahead of print]
  This intriguing case report tells the story of a man with ejaculatory pain that responded dramatically to topiramate (Topamax), with a dosage up to 150 mg/day. His doctors had him try topiramate after the usual neuropathic pain drugs didn’t help. Although the patient had a spinal cord injury, the authors suggested that this drug might be an option for ejaculatory pain in men with other conditions, such as chronic prostatitis/chronic pelvic pain syndrome. Many men with IC also have this type of pain.
  
  

• Hyaluronan Helps Long Term

  Engelhardt PF, Morakis N, Daha LK, Esterbauer B, Riedl CR. Long-term results of intravesical hyaluronan therapy in bladder pain syndrome/interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Oct 12. [Epub ahead of print]
  Hyaluronan, a glycosaminoglycan like heparin, is used for instillation in Europe. It seems to work well long term, based on these urologists’ survey of 70 of their patients. The clinicians surveyed their patients about the treatment because, so far, studies have looked only at more short term results. The mean follow-up for these patients was 4.9 years, and most (48 of 70) responded to the therapy. Initial pain scores went from 8 down to 3 after therapy and down further to 2 five years later. After five years, half the patients (24 of 48) reported complete remission of their bladder symptoms without any other therapy. For 42 percent (20 of 48), maintenance therapy improved symptom recurrence. Four patients reported no improvement. This was not a controlled study, which is needed for more definitive conclusions.
  
  

• Bladder Botox Helps

  Giannantoni A, Cagini R, Del Zingaro M, Proietti S, Quartesan R, Porena M, Piselli M. Botulinum A Toxin Intravesical Injections for Painful Bladder Syndrome: Impact Upon Pain, Psychological Functioning and Quality of Life. Curr Drug Deliv. 2010 Oct 15. [Epub ahead of print]
  Botulinum toxin A (Botox) injection into the bladder reduced pain and frequency significantly and also improved patients’ mental state and quality of life in this Italian study with 14 IC patients. Patients underwent one treatment with a dose of 200 U diluted in 20 mL of saline. The assessments were done three months later. Ten of the 14 patients said that their pain improved. In addition, their mean daytime and nighttime frequency went down significantly, and their quality-of-life and anxiety and depression scores improved significantly.
  
  

• Hyperbaric Oxygen Improves Bladder Blood Flow

  Hyperbaric oxygenation in combined treatment of interstitial cystitis. [Article in Russian] Urologiia. 2010 Jan-Feb;(1):22-4.
  In this Russian study, 116 IC patients got either their usual care or that plus 7 to 10 sessions in a hyperbaric oxygen chamber over 10 days. The usual therapy included antibiotics if there was infection, angioprotectors (drugs or supplements that improve blood flow, used in Russia), mast cell stabilizers, and bladder instillation with a combined solution (not specified). The abstract noted that Dopplerograms showed better blood flow in veins and arterioles in the bladder lining in the group that got the hyperbaric oxygen treatment and did not give any details on other measurements, such as pain, frequency, and urine volume. However, the authors stated that hyperbaric oxygen in the combined treatment of IC improves treatment results and promotes long-term remission.
  
  

• Neuromodulation Results with Tined Lead Hold Up Long Term

  Marcelissena TAT, Leonga RK, de Bieb RA, van Kerrebroecka PEV, de Wachtera SGG. Long-Term Results of Sacral Neuromodulation With the Tined Lead Procedure. J Urol. 2010 Nov;184(5):1997-2000.
  These urologists implanted nerve stimulators using the tined (fork-like) lead into 64 patients with either overactive bladder symptoms or urinary retention. The mean follow-up was nearly four and a half years. Based on voiding diaries, the authors claimed a success rate of 64 percent (38 of 59 patients). Twenty-one patients underwent a surgical revision, one patient had the leads removed and replaced because of migration, seven had the stimulator removed, and three stopped using it. Whether any of the patients had IC was not specified in the abstract.
  
  

• Topical Nifedipine a Bust for Vulvodynia

  Bornstein J, Tuma R, Farajun Y, Azran A, Zarfati D. Topical nifedipine for the treatment of localized provoked vulvodynia: a placebo-controlled study. J Pain. 2010 May 25. [Epub ahead of print]
  As interest grows in using topicals for pelvic pain, it’s important to put them to a rigorous test. Nifedipine, often used in a cream for chronic anal fissures, didn’t pass. This drug is a calcium channel blocker, used for angina and high blood pressure in its oral form. The researchers tested the topical for vulvodynia in a double-blind, placebo-controlled study with 30 vulvodynia patients. The patients used creams with 0.2 percent nifedipine, 0.4 percent nifedipine, or placebo at the vaginal entrance four times a day for six weeks. After treatment and three months later, all the groups reported reduced pain. This study highlights the need for controlled studies of topical therapies, said the authors.
  
  

• New Ways to Deliver Drugs in the Bladder Are on the Way

  Sarkar SG, Banerjee R. Intravesical drug delivery: Challenges, current status, opportunities and novel strategies. J Control Release. 2010 Sep 7. [Epub ahead of print]
  Delivering drugs right in the bladder has the potential to put medicine right where you need it in the amounts that will help. You’ve already read about liposomes and a drug-carrying device in our research coverage. But there’s more. To get medicine past the bladder lining barrier and into tissue, electromotive techniques and various substances are being tried. Electromotive enhancement, for example, is already being used in Europe in IC treatment. Chitosan and DMSO are used to temporarily disrupt the bladder lining. Nanotchnology may also lead to development of drug-encapsulated nanoparticles that improve chemical interactions with the bladder lining and enhance penetration of drugs into the bladder wall. Liposomes are nanocarriers, but gelatin nanoparticles, polymer nanoparticles, and magnetic particles are also being researched to enhance local drug concentrations in the bladder as well as to target diseased cells. Biomaterials that can stick to the bladder lining similar to the bladder’s own mucus layer could prevent a drug carrier from being washed away during voiding. Polymeric hydrogels have also been used to develop systems that gel as they warm in the body to deliver drugs into the bladder cavity.
  
  

• How IC Patients Actually Get Treated

  Anger JT, Zabihi N, Clemens JQ, Payne CK, Saigal CS, Rodriguez LV. Treatment choice, duration, and cost in patients with interstitial cystitis and painful bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Sep 2. [Epub ahead of print]
  What therapies are doctors actually using for IC, and how much does it costs? These researchers found out through a national insurance database, looking at claims made in 1999. Of the 533,910 insured adults, 89 had a diagnosis of IC with five years of follow-up. All patients got oral medications, 26 percent got bladder instillations, and 22 percent underwent hydrodistension. Total expenditures per patient were $2,808. Most of that expenditure was attributable to oral medications. Hydistention and bladder instillations were used in fewer than 25 percent of patients. Hydrodistension was used more frequently among newly diagnosed patients. These patterns, of course, may have changed since 1999.
  
  

• Researchers Learn Lessons on IC Experience from Drug Trial Data

  Nickel JC. Forensic dissection of a clinical trial: lessons learned in understanding and managing interstitial cystitis. Rev Urol. 2010 Spring;12(2-3):e78-85.
  A clinical trial for pentosan polysulfate (Elmiron) collected a great deal of information that’s answered more questions about IC than just treatment with this drug. It was unable to show that the potassium sensitivity test could predict a response to heparinoid therapy, such as with pentosan polysufate. It confirmed the O’Leary-Sant Interstitial Cystitis Symptom Index as a valid and sensitive outcome measure. It determined that doses of pentosan polysulfate higher than the standard FDA-approved dose of 300 mg per day did not increase efficacy, although it showed continuing the therapy for a long time increases the chances of controlling symptoms. It also showed that it is important to assess sexual dysfunction in IC patients and that successful IC therapy can improve sexual function. In addition, the data showed that symptom severity, quality of life, and sleep function are interrelated, and that improving IC symptoms improves sleep function and quality of life.
  
  

• Sacral Neuromodulation Results Still Good after Six Years

  Marinkovic SP, Gillen LM, Marinkovic CM. Minimum 6-year outcomes for interstitial cystitis treated with sacral neuromodulation. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Sep 17. [Epub ahead of print]
  Sacral neuromodulation results in IC are good six years after surgery, according to these urologists. They looked at the records of the 34 women they treated this way who had been followed up for a minimum of six years. The average Pelvic Pain and Urgency/Frequency (PUF) scores were 21.61 before surgery and 9.22 afterwards. The mean pain score before surgery was 6.5 out of 10, and at follow-up, it was 2.4. The average age of the women was 41, and they had been followed up for an average of about seven years.

Randomized Multicenter Clinical Trial Shows Efficacy of Myofascial Physical Therapy in Women with IC/PBS

Payne, C, Fitzgerald, MP, Burks, D, Nickel, C, Lukacz, E, Kreder, K, Chai, T, Hanno, P, Mayer, R, Yang, C, Peters, K, Foster, H, Landis, R, Cen, Propert, K, Kusek, J. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Now there’s proof that physical therapy can ease IC symptoms in women. The proof-of-concept study we reported on last year showed that this kind of study could be done, and now, the results of the larger trial are in. The study pitted myofascial physical therapy, aimed at the pelvic floor dysfunction that most IC patients have, against general, whole-body massage. Eighty-one IC patients with pelvic floor tenderness got up to 10 weekly treatments over 12 weeks and rated how they were doing before and after on a 7-point scale. They also rated their pain, urgency, and frequency and filled out the O’Leary-Sant IC Symptom and Problem Index questionnaires. Although all the patients had had symptoms for less than three years, nearly half (46 percent) had severe pain, and a little more than half (56 percent) had severe frequency. Fifty-nine percent of the group who got the myofascial physical therapy said they were moderately or markedly better, compared with 26 percent in the massage group, a significant difference. Although the other measures improved more for the women who got the myofascial physical therapy, the differences were not statistically significant. The most common adverse event for either therapy was pain. This is the first time in a decade of NIDDK-sponsored clinical trials in IC that there has been a positive result, pointed out the presenter, Dr. Payne.

6-Day Intensive Physiotherapy and Cognitive Behavior Clinic Treatment for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Anderson,R, Wise, D, Sawyer, T, Glowe, P. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
The controlled trial of pelvic physical therapy in men and women with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) or IC didn’t show benefit for men. But this study presenting long-term results of a similar program for men showed that physical therapy plus psychological training (the “Stanford protocol”) did help men. It was not, however, a controlled study. At the Stanford clinic, 125 men with severe, long-term symptoms (ongoing for an average of nearly eight years) underwent a six-week intensive program of physical therapy and psychological training in “paradoxical relaxation.” Many of the men learned how to do their own physical therapy. The investigators assessed how the men were doing from as little as one month to as much as nearly a year after their treatment. Fifty-two percent said their symptoms were moderately or markedly improved, while 11 percent indicated no change. Scores on a questionnaire assessing psychological benefits improved an average of about 14 out of 21 points. Sixty-seven percent of the men indicated they continue to use the cognitive training tapes and 47 percent the physical therapy. These results hold out hope for benefit with physical therapy for men with IC, despite the results of the controlled trial, which did not show significantly better results for pelvic floor-directed myofascial physical therapy than for general, whole-body massage in men.

Safety and Clinical Evaluation of Intravesical Liposome in Patients with Interstitial Cystitis/Painful Bladder Syndrome

Chuang, Y, Lee, W, Chiang, P. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
For a few years now, you’ve been hearing about research on liposomes—tiny, water-filled fat bubbles—in mice. But starting late last year, we began hearing about their use in actual IC patients in Taiwan. The first published study pitted weekly instillations against oral pentosan polysulfate (Elmiron), showing similar improvement. Now, the Taiwanese researchers have compared different schedules for liposome instillations. In an open-label study, that is, patients and doctors knew what they were getting or giving, some patients got instillations once a week and others twice a week for four weeks. The patients who got the instillations twice a week felt better faster. Each group showed improvement on the O’Leary-Sant IC Symptom and Problem Indexes and on pain and urgency scales at the end of the four weeks of treatment, but the twice-a-week group showed much more improvement. Four weeks after the instillations ended, the degree of improvement on these measurements was similar, but patients’ overall assessment of how they were doing showed those who had twice-a-week instillations still felt better. Cystoscopic pictures of their bladders told a dramatic story. The untreated bladders looked entirely red and inflamed, and the treated bladders started to look healthy. Liposomes may exert their calming effect in the bladder the way they do on skin, helping wounds heal and providing a barrier to irritants.

Intra-Trigonal Injection of Botox in Patients with Refractory Bladder Pain Syndrome Decreases Urinary Neurothrophins, Improves LUTS

Pinto, RA, Frias, B, Lopes, T, Silva, A, Silva, JA, Silva, CS, Dinis, P, Cruz, C, Cruz, Porto, F. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.

Last year, this team from Portugal presented research on a new approach to botulinum toxin A (Botox) injection into the bladder. This year, there were additional results, reflecting the team’s recently published study that you read about in the ICA’s e-Newswire. The results help support their different approach to bladder Botox, which uses a smaller amount of Botox than other procedures (100 U) and injects it into just the lowest part of the bladder, called the “trigone.” The procedure looks safe, it decreases symptoms for nine months, and retreatment is as effective as the first treatment. Moreover, levels drop of NGF, known to be elevated in IC patients’ urine, and of brain-derived neurotrophic factor, an NGF relative implicated in some neurologic diseases.

Submucosal Injection of Triaminolone for Hunner’s Ulcer Type IC

Thom, M, Lake, B, Royce, R, Klutke, C, American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Injecting Hunner’s lesions with steroid medication may prove to be a helpful, low-risk way to treat them. The most common method today is fulguration with an electrode or laser, although sometimes surgical excision, a riskier procedure, is still done. This team reported on their experience using injections of triamcinolone (Kenalog) in 58 IC patients with Hunner’s lesions. The injections are done through a cystoscope while the patient is under general anesthesia. Patients’ International Prostate Symptom Scores improved by about 9 points and Pelvic Pain Urgency/Frequency (PUF) scores by about 8 points, both significant differences. Also, on the Patient Global Impression of Change scale, most patients (66 percent) said they had “much improvement.” Forty-five percent of patients got a second set of injections at an average of a year later, with a similar degree of improvement. Getting a good result did not depend on a history of urinary tract infection or of having more than two Hunner’s lesions. The researchers are doing a comparative trial to see how this treatment stacks up against fulguration (which is also done cystoscopically with the patient under general anesthesia).

Tanezumab Reduces Pain and Urgency in Interstitial Cystitis: Results of a Phase 2 Trial

Evans, R, Moldwin, R, Cossons, N, Darekar, A, Mills, I. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Nerve growth factor (NGF) is thought to play roles in inflammation and in the immune response to injury, kicking pain hypersensitivity into gear and keeping pain signals going between the sensory nerves and the spinal cord. That results in the “central sensitization” thought to play a role in many chronic pain conditions, including IC. That’s why antibodies to NGF, which block its action, are being studied for a number of chronic pain conditions. One of these, tanezumab, is being tested in IC. In this proof-of-concept trial, patients got a one-time infusion of tanezumab or placebo. Patients who got tanezumab started with pain scores averaging 6.4 out of 10. After four weeks, their pain averaged 1.1 points better than scores for the patients who got placebo. (All the patients were able to continue their current IC and pain medications.) After six weeks, the scores averaged 1.4 points better. Ten weeks later, the effects had begun to wear off. Most of the urinary measurements—voided volume, frequency, and O’Leary-Sant IC Symptom Index scores—did not change significantly. Episodes of urgency, however, did. The most common adverse effect was abnormal tingling sensations, which went away for most patients by the end of the study, 16 weeks after the infusion. Although the average pain reduction was modest after this one-time dose, the results were good enough that a phase 2b trial with injections, rather than infusions, was begun. An osteoporosis trial with tanezumab, however, was stopped because of concerns about a bone side effect. The problem hasn’t been seen in other trials of tanezumab for other pain conditions. Nevertheless, no more IC patients are being recruited until the questions about the side effect are resolved.

Bladder Overactivity Suppressed by Electrical Stimulation of Foot

Chen,M, Shen, B, Wang, J, Liu, H, Roppolo, J, de Groat, W, Tai, C. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Could there be an even less invasive method than stimulation of the tibial nerve at the ankle to ease bladder symptoms? This team thinks so. Tibial nerve stimulation is done through a needle inserted at the ankle and requires patients to go to a clinic for each treatment. But just electrically stimulating the foot through a pad might work, the team surmised. They tried this in cats, who were under anesthesia. Some got irritating instillations, and some got neutral ones while they all got low- or high-frequency stimulation from a pad on the forefoot or hindfoot. Even low-frequency stimulation of the hindfoot inhibited reflex urination. Stimulation of the forefoot was not effective. The hindfoot stimulation also inhibited bladder overactivity and significantly increased bladder capacity. The effects did not persist beyond the stimulation period, however. Nevertheless, the team sees stimulation of nerves in the foot as a potential noninvasive neuromodulation treatment that patients could administer themselves.

Sacral Nerve Root Neuromodulation for the Treatment of Intractable PBS/IC: 14 Years Experience of One Center

Jerzy Gajewski, Ali Alzahrani, Halifax, Canada. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Long-term results of sacral neuromodulation (as with InterStim) in IC patients were good at this treatment center. Nevertheless, the revision rate was high. Of the 46 IC patients they treated with sacral neuromodulation, 72 percent (33 patients) improved at least 80 percent on a 7-point scale rating how they were doing. The patients were followed up for a median of about five years. Twenty-eight percent of patients had the devices removed, mainly because of poor outcome, and 50 percent of patients underwent reoperation. The most common reason for reoperation was that patients did not feel the stimulation and got worse. Battery life averaged nearly eight years. The best predictor of success, the researchers said, was being female and having urge incontinence. Urge incontinence, however, is thought to be uncommon in IC patients.

“Two-Stage-Implantation” vs. “Conventional Peripheral Nerve Evaluation – Response Rates in Sacral Nerve Stimulation

Bannowsky, A, Sugimoto, S, Böhler, G, van Ahlen, R, van Ahlen, H, Jünemann, K. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
At these treatment centers, patients got better results with sacral nerve stimulation (such as with InterStim) when they underwent a two-stage implantation procedure than when they got conventional test stimulation first. The conventional way is to test stimulation with temporary leads that can be removed easily. In the two-stage procedure, the permanent leads are implanted for the test, and then, if it works, the stimulator is implanted and connected to them. The 53 patients had various bladder conditions, including some who had pelvic pain. The procedure was successful for about half the patients who had the conventional test first (20 of 42). The response rate with the two-stage technique was 82 percent (9 of 11 patients). Patients showing the highest response rates were those who had neurogenic bladder (which often occurs in spinal cord injury) and overactive bladder.

The Predictors of Successful Hydrodistension Therapy in 399 Patients with IC in Japan

Hayami, H, Enokida, H, Kawagoe, M, Nakagawa, M, Naito, S, Matsumoto, T, Uozumi, J, Mimata, H, Takei, M. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Although it is falling out of favor in the United States, cystoscopy with hydrodistention is still a fairly common IC treatment in Japan. This Japanese team looked at the records of nearly 400 IC patients who underwent the treatment to see if any particular characteristics would predict success. Patients with fewer glomerulations (pinpoint bleeds in the bladder) had longer improvement than patients with more glomerulations. In addition, those that had bigger volumes of fluid (more than 500 mL) instilled and those under age 60 had longer improvement than patients who had lower volumes instilled or those who were older. The preliminary IC clinical guidelines from the American Urological Association, however, recommend avoiding high-pressure, long-duration hydrodistention; 60 to 80 cm (600 to 800 mL) of water is thought to be reasonable.

Pelvic Floor Injection of Botulinum Toxin A for Pelvic Pain: A Randomized, Controlled Pilot Study

Gottsch, H, Berger, R, Miller, J, Yang, C. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
Could botulinum toxin A (Botox) injection into the pelvic floor muscles help ease IC and chronic prostatitis/chronic pelvic pain syndrome (CPPS) symptoms? These researchers concluded no because their patients didn’t experience any significant improvement in pain scores. But, as urologists in the session pointed out, the team didn’t check patients first for pelvic floor muscle tenderness and did not inject Botox into pelvic muscle trigger points. Rather, they injected Botox in the same place in each patient—on either side of the urethra in women and into the bulbospongiosus muscle and superficial perineal muscles in men. Different studies need to be done to determine whether this therapy done a different way might be effective.

Choice and Outcomes of Alternative Therapies in Patients with IC/CPP

Baxter, C, Bolus, R, Mayer, E, Ackerman, D, Rodriguez, LV. American Urological Association (AUA) 2010 Annual Meeting, May 29 – June 3, 2010, San Francisco, CA.
In this study of alternative medicine use among 223 IC patients, analysis showed no significant improvement with or negative effects of any particular treatment.

• Treating One Internal Pain Can Ease Another

  Giamberardino MA, Costantini R, Affaitati G, Fabrizio A, Lapenna D, Tafuri E, Mezzetti A. Viscero-visceral hyperalgesia: Characterization in different clinical models. Pain. 2010 Jul 15. [Epub ahead of print]

  Having pain in more than one internal organ may make pain worse from each than it would be in people with pain coming from just one organ. The reason may be because of the neural “crosstalk” between organs that share neural pathways to the spinal cord and brain. That phenomenon may pump up the misery for IC patients who also have another chronic pain condition that affects internal organs, such as irritable bowel syndrome (IBS) or endometriosis. But the silver lining could be that easing pain from one condition might also calm the other. To test these ideas, this research team measured symptoms in patients who had one internal organ pain condition and in those who had two. They also looked at how successful treatment of one condition affected the other. (Although IC was not included, other conditions that often occur with IC and share neural pathways were.) The researchers found that patients with coronary artery disease and gallstones had more and more intense episodes of chest pains and gallstone pain and referred muscle pains than patients with either condition alone. Patients with IBS and painful periods had more intestinal pain, menstrual pain, and referred abdominal and pelvic muscle pain than patients with either condition alone. Results were similar for patients with urinary stones and menstrual pain. Treatment of one condition eased symptoms of the second in most patients. For example, hormonal therapy for painful periods or laser treatment for endometriosis also improved symptoms of urinary stones. In patients who had both gallstones and urinary stones on the left side, however, treatment of one did not ease pains from the other. That fits the theory because pain signals from these organs don’t travel the same neurologic pathway.
  
  

• Topiramate May Ease Painful Ejaculation

  Calabrò RS, Marra A, Quattrini F, Gervasi G, Levita A, Bramanti P. Central Neuropathic Pain: An Unusual Case of Painful Ejaculation Responding to Topiramate. J Sex Med. 2010 May 26. [Epub ahead of print]

  A man with spinal cord injury who had painful ejaculation got relief with topiramate (Topamax). The case may have implications for treating painful ejaculation in men with IC or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The patient wasn’t helped by treatment with more conventional neuropathic pain drugs, but when he got up to 150 mg daily of topiramate, the problem improved dramatically. Because he had a spinal cord injury, this man’s postejaculatory pain was likely generated in the central nervous system—a type of pain is thought to play a role in IC and CP/CPPS. Using topiramate for this purpose in men with IC or CP/CPPS may be worth study or even a try after you and your doctor weigh whether this treatment might be appropriate for you. Topiramate is approved for epilepsy and prevention of migraines but is used off label in pain management.
  
  

• Botox Injection Near Urethra Doesn’t Ease IC Pain

  Gottsch HP, Miller JL, Yang CC, Berger RE. A pilot study of botulinum toxin for interstitial cystitis/painful bladder syndrome. Neurourol Urodyn. 2010 Jun 29. [Epub ahead of print]

  This small trial of botulinum toxin A (Botox) injection on either side of the urethra in women with IC showed no difference between the treatment and placebo. The rationale for treatment was to block pain signals from the urethra and nearby tissues. At the recent American Urological Association meeting, where this study was presented, some urologists pointed out that this treatment was, in fact, a pelvic floor injection that was done without selecting patients who showed evidence of pelvic muscle problems on an exam. Evaluation of Botox injection to treat pelvic floor dysfunction will require a study of injection into pelvic floor muscle trigger points.
  
  

• Chondroitin Sulfate Instillation May be Promising

  Nickel JC, Egerdie RB, Steinhoff G, Palmer B, Hanno P. A Multicenter, Randomized, Double-blind, Parallel Group Pilot Evaluation of the Efficacy and Safety of Intravesical Sodium Chondroitin Sulfate Versus Vehicle Control in Patients With Interstitial Cystitis/Painful Bladder Syndrome. Urology. 2010 May 20. [Epub ahead of print]

  This placebo-controlled study of chondroitin sulfate instillation for IC hints that it could be effective, but it’s going to take a bigger study to prove it. Chondroitin sulfate is a glycosaminoglycan, as are heparin and pentosan polysulfate (Elmiron), but might cost less. This study included 65 patients who got weekly instillations with either 2.0 percent chondroitin sulfate in phosphate-buffered saline solution or an inactive placebo instillation. Based on patients’ judgment of being moderately or markedly improved, about 39 percent responded to the chondroitin compared with 23 percent to the placebo. Even though that’s nearly twice as many, the difference wasn’t statistically significant. A further, larger study needs to be designed, said the authors.
  
  

• Evidence Conflicts on Bladder Wall Botox for IC

  Tirumuru S, Al-Kurdi D, Latthe P. Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome/interstitial cystitis: a systematic review. Int Urogynecol J Pelvic Floor Dysfunct. 2010 May 7. [Epub ahead of print]

  Does injection of botulinum toxin A (Botox) into the bladder wall help tough cases of IC? It’s hard to tell because published results aren’t consistent. That’s why these authors analyzed the results of published, randomized, controlled trials and some other studies. Eight out of 10 studies reported improvement in symptoms, but there were some complications such as painful urination and difficulty urinating: 19 out of 260 patients had to use a catheter to void. The authors concluded that the studies show a trend toward short-term benefit but that clinicians should wait for more evidence.
  
  

• Best Approach for Botox May Be Lower Bladder Only

  Pinto R, Lopes T, Frias B, Silva A, Silva JA, Silva CM, Cruz C, Cruz F, Dinis P. Trigonal Injection of Botulinum Toxin A in Patients with Refractory Bladder Pain Syndrome/Interstitial Cystitis. Eur Urol. 2010 Mar 6. [Epub ahead of print]

  A limited number of botulinum toxin A (Botox) injections into the lower part of the bladder produced long-lasting results for IC patients with few side effects. This may turn out to be a better approach than previous techniques, which usually inject more Botox over more of the bladder wall. These urologists presented some of their results at the annual American Urological Association meeting in 2009, which we reported on then. Now, their paper has been published. This study wasn’t a controlled trial, but an exploratory one where the urologists tried this technique of injecting a total of 100 U of Botox injected into 10 sites in the trigone. The researchers assessed the results with pain scales, voiding diaries, O’Leary-Sant and quality of life scores and urodynamic tests one month later, three months later, and every three months thereafter. The researchers also measured levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). All the measures improved at one and three months. The amount the bladder filled before patients felt pain and the maximum bladder capacity more than doubled. For more than half the patients, treatment remained effective for nine months. Retreatment was also effective in all cases, with similar duration. A significant, transient reduction in urinary NGF and BDNF was observed. No cases of voiding dysfunction, such as retention, occurred.
  
  

• Minimally Invasive Treatments Are IC Mainstays

  Wehbe SA, Fariello JY, Whitmore K. Minimally Invasive Therapies for Chronic Pelvic Pain Syndrome. Curr Urol Rep. 2010 May 7. [Epub ahead of print]

  A complex of symptoms calls for more than one therapy, so combining minimally invasive ones can be helpful for IC and chronic prostatitis/chronic pelvic pain syndrome. The authors reviewed what is known about the minimally invasive treatments available, including dietary modifications, physical therapy, mind-body therapies, medical therapy, intravesical therapies, trigger point injections, botulinum toxin injections to the pelvic floor, and neuromodulation.
  
  

• Palmidrol May Relieve Neuropathic Pelvic Pain

  Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. Misdiagnosed Chronic Pelvic Pain: Pudendal Neuralgia Responding to a Novel Use of Palmitoylethanolamide. Pain Med. 2010 Mar 22. [Epub ahead of print]

  In this case report from Italy, a patient with chronic pelvic pain caused by pudendal neuralgia was treated successfully with palmitoylethanolamide (also known as palmidrol or PEA). It may relieve the pain by acting on receptors in pain pathways in the nervous system and by acting directly on mast cells. The authors said that animal studies suggest palmidrol could be a valuable pharmacological alternative to some drugs, such as antiepileptics and antidepressants, that are commonly used to treat neuropathic pain. The compound is an ingredient in a veterinary supplement for lower urinary tract symptoms in dogs and cats.
  
  

• Intravaginal E-stim Helpful for Pelvic Pain

  de Bernardes NO, Marques A, Ganunny C, Bahamondes L. Use of intravaginal electrical stimulation for the treatment of chronic pelvic pain: a randomized, double-blind, crossover clinical trial. J Reprod Med. 2010 Jan-Feb;55(1-2):19-24.

  This small but well-controlled trial showed that intravaginal electrical stimulation was helpful for unexplained pelvic pain. The double-blind, crossover, randomized clinical trial included 26 women randomly assigned to start with active treatment of sham treatment comprising 10 30-minute, twice-weekly sessions. Then, the treatment was switched for another 10 sessions. Five of 11 women who started with the sham treatment had pain scores greater than 3 on a 0-to-10 scale, but when they got the active treatment, only one had a pain score that high. Among the 16 women who started with active treatment, 2 had a score greater than three at the end of that treatment, but then after the sham treatment, 3 did. After both sessions were over, 54.6 percent of the women who started with sham treatment and 80 percent of those who started with active treatment had a pain score less than 3.
  
  

• Phenotyping System Could Target Therapies, Improve Studies

  Nickel JC. A new approach to understanding and managing chronic prostatitis and interstitial cystitis. Rev Urol. 2010 Winter;12(1):67-8.

  This review summarizes the research so far on the UPOINT “phenotyping” or classification system for the urologic pelvic pain syndromes IC and chronic prostatitis/chronic pelvic pain syndrome. Assessing whether patients have urinary, psychosocial, organ-specific, infection, neurologic/systemic, or tenderness symptoms should help improve the diagnosis, treatment, and study of IC. Knowing what set of symptoms a patient has could help a clinician decide what combination of therapies would fit best. In addition, the system would help show which patients in a trial might benefit from a therapy when the therapy isn’t one-size fits all.
  
  

• What Evidence Backs Which Pelvic Pain Treatments?

  Green IC, Cohen SL, Finkenzeller D, Christo PJ. Interventional therapies for controlling pelvic pain: what is the evidence? Curr Pain Headache Rep. 2010 Feb;14(1):22-32.

  This review article argues for a multidimensional approach to treating chronic pelvic pain, using both pain treatment and treatment aimed at the causes or presumed causes. Most often, treatment requires a combination of these. The conditions covered in the article include endometriosis, interstitial cystitis, pelvic adhesive disease, adenomyosis, and pelvic venous congestion.
  
  

• Spinal Cord Stimulation Eases Visceral Pain

  Kapural L, Nagem H, Tlucek H, Sessler DI.

  Spinal Cord Stimulation for Chronic Visceral Abdominal Pain. Pain Med. 2010 Jan 15. [Epub ahead of print] Spinal cord stimulation relieves visceral pain at least 50 percent in a majority of patients treated by these pain specialists. They tried stimulation, usually applied at the level of the fifth thoracic vertebra (in the upper back), in 36 patients who had either visceral pain (in 32 patients), central pain (3 patients), or mixed visceral and central pain (3 patients). (Bladder pain is a type of visceral pain.) Both pain levels and opioid use went down significantly. Patients were treated from 4 to 14 days (an average of 9). Thirty of the 35 (86%) got at least 50% pain relief, with pain scores dropping from an average of 8 to 3 points on a 10-point scale and opioid medication use dropping from the equivalent of 110 of morphine a day to 70 mg. Seven patients had devices removed because of infection or lead migration. Among the 19 patients who had a permanent implant and were followed up for at least a year, pain scores remained low, at an average of about 4, and opioid use was down to an average of 38 mg of morphine equivalents per day.
  
  

• Spinal Cord Stimulation Techniques for Visceral Pain

  Kapural L, Deer T, Yakovlev A, Bensitel T, Hayek S, Pyles S, Khan Y, Kapural A, Cooper D, Stearns L, Zovkic P. Technical Aspects of Spinal Cord Stimulation for Managing Chronic Visceral Abdominal Pain: The Results from the National Survey. Pain Med. 2010 Mar 4. [Epub ahead of print]

  How are most pain management specialists doing spinal cord stimulation for visceral pain? To find out, these pain management specialists surveyed their colleagues who are doing spinal cord stimulation for abdominal pain. The cases they gathered included 43 female and 27 male patients. Test stimulation was tried for an average of about 5 days with the leads positioned at the level of the fifth or sixth thoracic vertebra (T5 or T6). The test stimulation didn’t work for four patients. Sixty-six patients had at least 50 percent pain relief, with levels going from about an 8 to about a 2 on a 10-point scale. Patients use of opioids dropped from the equivalent of 128 mg of morphine a day to 79 mg. For the permanent implant, most of the surgeons used two octrode-type leads, which have eight separate stimulation areas and can cover an area of the spinal cord about two spinal segments long, position at the T5 to T6 level. With an average follow-up of 84 weeks, pain scores went from about 8 to about 2 and opioid use dropped from the equivalent of 158 mg of morphine a day to 36. The authors concluded that spinal cord stimulation to treat abdominal visceral pain may give patients significant, long-term improvements in pain and help them reduce their use of opioids.
  
  

• Zen Steels Against Pain . . .

  Grant JA, Rainville P. Pain sensitivity and analgesic effects of mindful states in Zen meditators: a cross-sectional study. Psychosom Med. 2009 Jan;71(1):106-14. Epub 2008 Dec 10.

  Meditation has long been recommended to pain patients. Now, there’s some concrete evidence to show that if you practice meditation, you can help control pain. When 13 highly trained Zen meditators (who have had more than 1,000 hours of practice) and 13 control volunteers had heat applied to their calf, meditators needed much higher temperatures to produce pain. When the two groups followed instructions to observe the sensations from their calf moment to moment in a nonjudgmental way (a mindfulness meditation practice), the Zen meditators felt their pain go down, whereas the controls did not. Experienced meditators demonstrated an average 18 percent reduction in perceived pain intensity compared with controls.
  
  

• . . . By Thickening the Brain

  Grant JA, Courtemanche J, Duerden EG, Duncan GH, Rainville P. Cortical thickness and pain sensitivity in Zen meditators. Emotion. 2010 Feb;10(1):43-53.

  How does meditation work for pain? Maybe by thickening the brain. The same group of researchers who showed that experienced Zen meditators can withstand more pain and are able to reduce pain levels with their practice also found that the regular meditators had thicker brain regions responsible for processing pain and emotion than nonmeditators. Magnetic resonance imaging (MRI) showed the experienced meditators had lower pain sensitivity. Among all the volunteers, lower pain sensitivity correlated with having a thicker cortex in the anterior cingulate, bilateral parahippocampal gyrus, and anterior insula. Specifically, the meditators had a thicker cortex in the dorsal anterior cingulate and bilaterally in secondary somatosensory cortex. The more years of meditation experience they had, the thicker the gray matter in the anterior cingulate was.
  
  

• Botox for Bladder Bottom Only

  Pinto R, Lopes T, Frias B, Silva A, Silva JA, Silva CM, Cruz C, Cruz F, Dinis P. Trigonal Injection of Botulinum Toxin A in Patients with Refractory Bladder Pain Syndrome/Interstitial Cystitis. Eur Urol. 2010 Mar 6. [Epub ahead of print]

  Department of Urology, Hospital de São João, Portugal; Faculty of Medicine, University of Porto, Portugal. 
  
  Injecting botulinum toxin A (Botox) just in the lower part of the bladder looks like a promising IC therapy. This study by urologists in Portugal, which we reported on from the 2009 American Urological Association meeting, has now been published. The urologists treated women who had IC and who didn’t respond to other treatment with injections of 100 U of Botox at 10 sites in the lower triangle of the bladder, called the trigone. One and three months later, all said that they had improved. Pain, daytime and nighttime frequency, scores on the O’Leary-Sant Symptom and Problem Index, and quality of life all improved significantly. The amount of urine patients could hold before they felt pain doubled. The effects lasted at least nine months for more than half the patients. Retreatment worked for all of them, with a similar length of relief. None of the women had any difficulty urinating, such as urinary retention. The investigators also measured levels of nerve growth factor and brain-derived neurotrophic factor, which may play a role in bladder pain. After treatment, levels went down significantly for a short time. Larger, placebo-controlled studies are needed to help confirm that this is a safe and effective treatment.
  
  

• Antidepressants for IC Still Need Scientific Support

  Papandreou C, Skapinakis P, Giannakis D, Sofikitis N, Mavreas V. Antidepressant drugs for chronic urological pelvic pain: an evidence-based review. Adv Urol. 2009;2009:797031. Epub 2010 Feb 14.

  Scientific support for using antidepressants other than amitriptyline in IC is still weak. These pain management specialists combed through the literature for studies on antidepressants used for urological chronic pelvic pain (which also includes chronic prostatitis/chronic pelvic pain syndrome). The 10 studies that met their analytic criteria included 360 patients and concerned amitriptyline (Elavil), sertraline (Zoloft), duloxetine (Cymbalta), nortriptyline (Pamelor), and citalopram (Celexa). Only 4 of the 10 studies were randomized controlled trials (2 for amitriptyline, 2 for sertraline), which had mixed results. Amitriptyline seems to have the best support. On the other hand, the drugs were generally well tolerated, and no serious side effects were reported.
  
  

• Botox Eases Vulvar Symptoms

  Bertolasi L, Frasson E, Cappelletti JY, Vicentini S, Bordignon M, Graziottin A. Botulinum neurotoxin type A injections for vaginismus secondary to vulvar vestibulitis syndrome. Obstet Gynecol. 2009 Nov;114(5):1008-16.

  When other treatments fail to work, botulinum toxin A (Botox) injection into a pelvic floor muscle can offer big relief for vaginal spasm and pain. Vulvar vestibulitis is fairly common in women with IC. Sometimes, vulvar vestibulitis is accompanied by vaginismus, which is spasm of the muscles around the vagina, making sexual intercourse difficult and painful. These gynecologists injected Botox, guided by diagnostic electromyogram (EMG) recordings, into one of the pelvic floor muscles, called the levator ani, in 29 women who weren’t helped by other medical and behavioral therapy. At the beginning of the study and four weeks after getting an injection, the women were asked about sexual intercourse, underwent EMG testings and vaginal examinations, rated their pain, filled out questionnaires about female sexual function and quality of life, and underwent a bowel and bladder symptom assessment. Four weeks after injection, their ability to have sexual intercourse and their levator ani EMG hyperactivity improved, as did the other measurements. The benefits lasted through more cycles of injection. When follow-up was over, 63 percent of the patients had completely recovered from vaginismus and vulvar vestibular syndrome, 15 percent still needed reinjections, and 15 had dropped out. The abstract did not note whether any of the patients had IC.
  
  

• Amitriptyline Sustains Results in IC

  Hertle L, van Ophoven A. Long-term results of amitriptyline treatment for interstitial cystitis. Aktuelle Urol. 2010 Jan;41 Suppl 1:S61-5. Epub 2010 Jan 21.

  Nearly two-thirds of IC patients respond to amitriptyline (Elavil) treatment over the long-term. The same researchers that first published a controlled study of amitriptyline for IC have now carried out their studies longer, with encouraging positive results. The study patients took from 12.5 to 150 mg (average 55 mg) at night, starting with low doses and increasing them to what they were comfortable with. The researchers followed up the patients for an average of 19 months. Sixty-four percent of the patients said they were better overall, and 46 percent said their satisfaction with the results was either excellent or good. Eighty-four percent of patients experienced side effects (mostly dry mouth and weight gain). About a third of the patients dropped out of the study after an average of 6 weeks at a mean dosage of 70 mg/day, but the main reason was because their symptoms didn’t respond; only about four percent of patients dropped out because of side effects. Long-term treatment with amitriptyline is feasible, safe, and effective, provided that the drug is used judiciously to minimize side effects, concluded the researchers.
  
  

• Use of Neurostimulation for Pain Growing

  Mekhail NA, Cheng J, Narouze S, Kapural L, Mekhail MN, Deer T. Clinical Applications of Neurostimulation: Forty Years Later. Pain Pract. 2010 Jan 8. [Epub ahead of print]

  Applications of neurostimulation to manage pain are growing, especially in visceral pain and IC in particular. Technologic advances in neurostimulation are bringing new hope for patients with chronic pain conditions that don’t respond well to other treatments. Support for the benefit of neurostimulation is strong in a number of conditions, including complex regional pain syndromes and vascular diseases. “A growing body of literature supports neurostimulation for visceral pain in general and interstitial cystitis in particular,” these anesthesiologists wrote. They called for more, carefully designed research to establish evidence-based application of neuromodulation in new conditions. This article is available online at www.aapainmanage.org.
  
  

• Acupuncture Shows Potential for Chronic Pelvic Pain

  Tugcu V, Tas S, Eren G, Bedirhan B, Karadag S, Tasci A. Effectiveness of Acupuncture in Patients with Category IIIB Chronic Pelvic Pain Syndrome: A Report of 97 Patients. Pain Med. 2010 Jan 22. [Epub ahead of print]

  Acupuncture seems to ease pain and urinary symptoms in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), holding out hope for IC, too. This was not a controlled study, so it can’t bring definite conclusions. Nevertheless, nearly all the men in this study got significantly better after six weekly sessions of acupuncture to the BL-33 acupoints. The men completed the NIH Chronic Prostatitis Symptom Index questionnaire before and after treatment and 12 and 24 weeks later. Of the 93 men, 86 (92 percent) had a better than 50 percent decrease in their total scores. The reductions were significant in all the subscores—pain, urinary symptoms, and quality of life.
  
  

• Bladder Botox Injection Called Ineffective

  Miyagawa I, Watanabe T, Isoyama T, Honda M, Kobayasi N, Hikita K, Saito M, Hirakawa S. Experience with injections of botulinum toxin type A into the detrusor muscle. Aktuelle Urol. 2010 Jan;41 Suppl 1:S24-6. Epub 2010 Jan 21.

  These Japanese urologists tried injection of botulinum toxin A (Botox) into the bladder for overactive bladder (OAB) and a few IC patients, but didn’t see positive effects in their IC patients. The urologists injected from 100 to 300 IU of the toxin into the bladder muscle of 30 patients, four of whom had IC, and then followed them up 4, 12, and 36 weeks later. The injections were judged effective for nearly all patients with neurogenic OAB and nonneurogenic OAB. But the injections were not effective in their IC patients. None of the patients experienced adverse effects. These results are contrary to some other studies on bladder Botox injections.
  
  

• Valium Suppositories Help Ease Pelvic Floor Dysfunction

  Rogalski MJ, Kellogg-Spadt S, Hoffmann AR, Fariello JY, Whitmore KE. Retrospective chart review of vaginal diazepam suppository use in high-tone pelvic floor dysfunction. Int Urogynecol J Pelvic Floor Dysfunct. 2010 Jan 12. [Epub ahead of print]

  Creative IC clinicians have been using intravaginal diazepam (Valium) for some time to help ease pelvic floor dysfunction, but now, a study supports the practice. In this study, the researchers looked at 26 patients’ charts to see whether the suppositories made a difference for them. The patients all had high-tone pelvic floor dysfunction and sexual pain. Twenty-five of the 26 said the suppositories helped them, and six of the seven sexually active patients were able to resume intercourse. The patients’ scores on Female Sexual Function Index and their pain ratings improved, although not in a statistically significant way. But their measured pelvic floor muscle tone did improve significantly. From this preliminary assessment, the investigators concluded that the intravaginal diazepam suppositories gave clinically significant improvement compared with usual treatment alone, but the team plans to do a prospective, randomized, placebo-controlled, multicenter study on intravaginal diazepam. You can read about this and more topical treatments that ease pain in the upcoming Winter 2010 issue of the ICA Update .
  
  

• Physical Therapy Can Get Pelvic Floor Back to Normal

  Gentilcore-Saulnier E, McLean L, Goldfinger C, Pukall CF, Chamberlain S. Pelvic Floor Muscle Assessment Outcomes in Women With and Without Provoked Vestibulodynia and the Impact of a Physical Therapy Program. J Sex Med. 2010 Jan 6. [Epub ahead of print]

  Objective measurements showed the pelvic floor physical therapy can bring the muscles back to normal. The researchers compared measurements of pelvic floor muscle behavior in 11 women with provoked vestibulodynia (PVD), which is pain specifically at the vagina, and 11 control women. The women with PVD got eight treatment sessions of manual therapy, biofeedback, electrical stimulation, dilator insertions, and home exercises. All the women underwent surface electromyography recording, which measures muscle activity, and manual assessments by the therapists. The tests showed that women with PVD had higher activity in their superficial pelvic floor muscles than the healthy women, but not in the deep pelvic floor muscles. Both groups of women’s pelvic floor muscles (mainly the superficial muscles) responded to painful pressure, although the women with PVD reacted more. Women with PVD also had higher pelvic floor muscle tone (tightness), decreased flexibility, and decreased relaxation capacity. After treatment, the women with PVD responded less to pain and had less muscle tightness, improved muscle relaxation capacity, and better vaginal flexibility—so much so that those measurements were the same as in the control women.*
  
  

• Pain Management Critical

  Hanno P, Lin A, Nordling J, Nyberg L, van Ophoven A, Ueda T, Wein A. Bladder Pain Syndrome Committee of the International Consultation on Incontinence. Neurourol Urodyn. 2010;29(1):191-8.

  “Pain management is critical throughout the treatment process,” said this international committee, which made new recommendations on IC terminology, diagnosis, and treatment based on developments in the last four years. The Bladder Pain Syndrome Committee of the International Consultation on Incontinence decided to use the name “bladder pain syndrome” and recommended that the first clinical assessment should include a frequency/volume chart, focused physical examination, urinalysis, and urine culture. They recommended that treatment progress from conservative approaches through various oral and bladder (instillation) therapies, reserving surgery mainly for cases that don’t respond to other treatment. The committee believes IC is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder.
  
  

• Hyaluronan Instillation Works Better than Heparin

  Shao Y, Shen ZJ, Rui WB, Zhou WL. Intravesical Instillation of Hyaluronic Acid Prolonged the Effect of Bladder Hydrodistention in Patients With Severe Interstitial Cystitis. Urology. 2009 Dec 16. [Epub ahead of print]

  In IC patients with small bladder capacity, instillation of hyaluronan after cystoscopy and hydrodistention worked better than heparin. The 47 patients in this study all had functional bladder capacities under 200 mL (about 7 ounces) and underwent hydrodistention. Then, 20 patients got instillation of 40 mg hyaluronan once a week for the first month and then once a month for two months, 16 got heparin instead, and 11 got hydrodistention alone. (Both heparin and hyaluronan are types of glycosaminoglycans or GAGs.) Three months later, the group that got hydrodistention alone wasn’t better. Six and nine months later, the hyaluronan group had a greater rate of improvement than the heparin group (77.8 versus 33.3 percent at six months and 50 versus 20 percent at nine months). Nine months later, the improvements were slight but still statistically significant in the hyaluronan group.
  
  

• Treating Hunner’s Ulcers Brings Relief

  Payne RA, O’Connor RC, Kressin M, Guralnick ML. Endoscopic ablation of Hunner’s lesions in interstitial cystitis patients. Can Urol Assoc J. 2009 Dec;3(6):473-7.

  A formal study now confirms what many know—that treating Hunner’s ulcers can bring relief. Removing the ulcers, which is usually done by “burning” them off, produced a better-than-50 percent improvement in 12 and total improvement in 8 out of 14 patients. The mean improvement was 76 percent. Four patients had a recurrence, but after repeat treatment, they all improved. The authors made the point that ulcers should be retreated when symptoms recur. IC patients and clinicians should soon learn about the results of a study of a new technique to treat Hunner’s ulcers—injection of a steroid—and how the results compare with the current techniques, which include fulguration (cautery with a heated instrument), laser treatment (“burning off” with a laser beam), and excision (cutting the ulcer out).
  
  

• Doctors Take Dim View of Hydrodistention

  Mahendru AA, Al-Taher H. Cystodistension: certainly no standards and possibly no benefits-survey of UK practice. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Nov 10. [Epub ahead of print]

  When hydrodistention is called for and whether it is really beneficial and safe are still in question, according to these gynecologists. They surveyed gynecologists, urologists, and urogynecologists in the United Kingdom to find out what conditions the procedure was being used for, how it was being done, and what benefits and complications the doctors saw. Most commonly, the procedure is used for IC diagnosis and treatment, followed by low bladder capacity and overactive bladder. Nearly all respondents used short-term (less than 20 minutes) distension. The lack of standardization was apparent, and further research is needed before any conclusions about its benefits and safety can be made, wrote the authors.
  
  

• New Type of Drug and H2 Antihistamines Take Down Pelvic Pain

  Rudick CN, Schaeffer AJ, Klumpp DJ. Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis. BMC Urol. 2009 Nov 12;9(1):16. [Epub ahead of print]

  A neurokinin-1 receptor blocker—a new type of drug—and H2-type antihistamines reduced or even stopped pelvic pain in an experimental model of nerve-generated IC. Mice that have a pseudorabies virus infection develop a nerve-generated cystitis with proliferation of mast cells and pelvic pain that looks a lot like IC. These investigators tried administering a number of drugs to these mice and tested their pain reactions to touch on their abdomens. An NK-1 blocker, known so far only as L-703606, and the histamine-2 blockers ranitidine (Zantac), famotidine (Pepcid), and cimetidine (Tagamet) reduced or stopped pelvic pain. On the other hand, other drugs tested (some used in IC) had no effect on the pain, including hydroxyzine (Atarax, Vistaril), proton pump inhibitors (such as omeprazole or Prilosec), a trigger of histamine receptor 3, and gabapentin (Neurontin). So far, FDA has approved one NK-1 blocker, aprepitant (Emend), has been for marketing. It is used for chemotherapy-induced nausea and vomiting. The NK-1 receptor is found in many tissues, including the nervous system and genitourinary tract, and research on NK-1 blockers has also been aimed at pain.

• Sacral Stimulators for IC Called Successful, but Half Are Removed

   

  Powell CR, Kreder KJ. Long-Term Outcomes of Urgency-Frequency Syndrome Due to Painful Bladder Syndrome Treated With Sacral Neuromodulation and Analysis of Failures. J Urol. 2009 Nov 12. [Epub ahead of print]

  Urologists at the University of Iowa said long-term benefit of sacral stimulators for their IC patients was good. Nevertheless, half the implanted stimulators had to be removed. From January 2000 to July 2004, the urologists did test stimulation (some with the temporary lead and later some with the permanent lead) on 32 women and 7 men with IC and implanted permanent generators in 22 patients. The average follow-up was about five years, and the authors said long-term success was similar with the different leads—92 percent (12 of 13) in patients who got the temporary lead and 78 percent (7 of 9) in those who got the permanent lead. In the 17 patients who complained of painful urination or pelvic pain, 65 percent (11) had their pain cured. Of the 22 patients who got permanent generators, 14 percent (3) lost benefit over time. In the other patients who had devices removed, the reasons were battery depletion, device malfunction, and infection. 
   

• Bladder Botox Injections Show Benefit

  Giannantoni A, Mearini E, Del Zingaro M, Proietti S, Porena M. Two-Year Efficacy and Safety of Botulinum a Toxin Intravesical Injections in Patients Affected by Refractory Painful Bladder Syndrome. Curr Drug Deliv. 2009 Oct 29. [Epub ahead of print]

  In 13 women with IC who have been followed up for two years, botulinum toxin A (Botox) injections into the bladder have been beneficial. On average, each woman got five injections of 200 U, averaging about five months apart. Ten patients noted their symptoms improved when they were seen one and four months after getting treated. One month after injection, nine patients had painful urination, and four months later, seven did. Three patients who felt no effect after the first treatment session had another treatment three months later with satisfactory results. The patients have been followed up for two years, and beneficial effects have persisted. The researchers concluded that bladder Botox injection is effective and safe in the “medium term” and noted that the beneficial effects decrease a few months after treatment, so repeat injections are needed. 
   

• Pudendal Nerve Stimulation Can Help when Sacral Doesn’t

  Peters KM, Killinger KA, Boguslawski BM, Boura JA. Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms. Neurourol Urodyn. 2009 Sep 28. [Epub ahead of print]

  Urologists at William Beaumont Hospital in Royal Oak, Michigan, have been trying a different approach to neurostimulation in IC and overactive bladder patients, targeting the pudendal nerve rather than one of the sacral nerves. This summary of their results in 84 patients indicates that the approach can be helpful even after the more common sacral neuromodulation stops working or doesn’t work. The approach uses a lead that is implanted near the pudendal nerve in the ischiorectal fossa, an area between the anus and “sit bones.” Sixty of the 84 patients (71 percent) had more than 50 percent improvement in symptoms, although 5 decided to have sacral neuromodulation. Nearly all (93 percent) patients who had had sacral neuromodulation fail responded to the pudendal nerve stimulation. There were seven complications requiring five revisions, and there were also four other reoperations. Five devices were taken out. The improvements in frequency, voided volume, incontinence, and urgency were significant. The abstract also noted improvement in pelvic pain. More research is needed to assess how this therapy does over the long term and to predict which patients will have success with it, noted the authors.

• Chondroitin Latches onto Damaged Bladder Lining

  Hauser PJ, Buethe DA, Califano J, Sofinowski TM, Culkin DJ, Hurst RE. Restoring Barrier Function to Acid Damaged Bladder by Intravesical Chondroitin Sulfate. J Urol. 2009 Sep 16. [Epub ahead of print]

  Chondroitin sulfate bladder instillations may work by latching on tight to damaged areas of the bladder lining, which restores the barrier function. Chondroitin sulfate instillation is in clinical trials in the United States and is approved for marketing in Canada and Europe. But how it might work is still being researched, and these urologists took a look at its actions on the microscopic level. In mouse bladder lining tissue damaged by acid, the chondroitin sulfate bound tightly—and only—to the damaged bladder surface. In addition, the chondroitin sulfate restored bladder permeability (“leakiness”) to normal. That, concluded the researchers, suggests that the glycosaminoglycan layer is a major contributor to the barrier function of the bladder lining. The dose used for instillation in humans in Canada (400 mg per instillation) is enough to achieve maximum efficacy, the authors said.

• European Association of Urology Issues Chronic Pelvic Pain Guidelines

  Fall M, Baranowski AP, Elneil S, Engeler D, Hughes J, Messelink EJ, Oberpenning F, de C Williams AC. EAU Guidelines on Chronic Pelvic Pain. Eur Urol. 2009 Aug 31. [Epub ahead of print]

  The European Association for Urology issued guidelines on diagnosis and treatment of all types of chronic pelvic pain, including chronic prostate and bladder pain syndromes, urethral pain, scrotal pain, pelvic pain in gynecologic practice, and neurogenic dysfunction. The guidelines also address the role of the pelvic floor and pudendal nerve, psychological factors, general treatment of chronic pelvic pain, nerve blocks, and neuromodulation. The journal article is a summary, but the full guidelines are available online at www.uroweb.org.

• Anesthetic Instillation Improves Pain, Frequency

  González PA, Ruiz JI, Cubillana PL, Iñiguez GD, Morcillo JC, Albacete MP. New approach in treatment of pelvic chronic pain syndrome (CPPS). [Article in Spanish] Actas Urol Esp. 2009 Jun;33(6):681-5.

  Instillation of a steroid, anesthetic, and antibiotic solution eased pain and frequency for patients at a clinic in Spain, where instillation is a new therapeutic option. Patients’ pain dropped from an average scores of 6.4 out of 10 at the start to 4.7 at one month and 2.4 at six months, with 75 percent of patients showing their pain was better. Frequency dropped from 22.5 times a day to 16.2 times at one month and 13.5 times at 6 months. Patients also rated how they were doing overall, with 30 percent saying they were much better, 30 percent moderately better, and 10 percent slightly better. (The abstract did not state how often instillations were given.)

• Botox So Far

  Rao A, Abbott J. Using botulinum toxin for pelvic indications in women. Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):352-7.

  This literature review for gynecologists concludes that the conditions mostly likely to be improved by botulinum toxin (Botox) therapies are pelvic floor spasm, daily pelvic pain, and pain with intercourse. Botox also improves pain scores for provoked vestibulodynia (a type of vulvodynia), although data are limited. Randomized, controlled trials show there is a role for Botox in managing idiopathic detrusor overactivity (a type of overactive bladder), although long-term follow-up data are lacking. Potential problems with Botox injection include toxin reactions, urinary and fecal incontinence, urinary retention, and secondary treatment failure because of antibody production. The article did not discuss IC.

• Multimodal Approach Helpful, but Needs Updating

  Hanley RS, Stoffel JT, Zagha RM, Mourtzinos A, Bresette JF. Multimodal therapy for painful bladder syndrome / interstitial cystitis: pilot study combining behavioral, pharmacologic, and endoscopic therapies. Int Braz J Urol. 2009 Jul-Aug;35(4):467-74.

  Patients improved in a pilot study by some US urogynecologists of multiple therapies for IC, but the treatments were not the most modern or helpful by today’s standards. The urogynecologists used well-accepted techniques such as diet modification and timed voiding but also used daily antibiotics, Kegel exercises, and hydrodistention under anesthesia. Most IC experts today do not prescribe antibiotics unless a patient has a proven UTI. Kegel exercises are aimed at strengthening the pelvic floor muscles, but most IC expert physicians and physical therapists recognize that relaxation of the pelvic floor needs to be the aim of physical therapy at the beginning. Although hydrodistention may be helpful, many IC experts prefer other therapies first and use hydrodistention early only to make sure that other bladder conditions are not causing symptoms.

• Instilled Liposomes Beat Elmiron in First IC Patient Trial

  Chuang YC, Lee WC, Lee WC, Chiang PH. Intravesical Liposome Versus Oral Pentosan Polysulfate for Interstitial Cystitis/Painful Bladder Syndrome. J Urol. 2009 Aug 13. [Epub ahead of print]

  Liposomes beat pentosan polysulfate (Elmiron) in this first published study of liposomes instilled into the bladder in actual IC patients. Liposomes are tiny fat-like bubbles that may coat or soothe the irritated bladder lining, and they have been researched for some time in animal models of IC. In this small study in Taiwan, the urologists compared instillation of liposomes (80 mg/40 cc distilled water) once a week for four weeks with Elmiron (100 mg) three times a day for four weeks in 12 patients each. The investigators evaluated how patients were doing at the beginning and at four and eight weeks after treatment started. Frequency and nocturia went down significantly in each group, but patients who got the liposomes also had significant decreases in pain, urgency, and scores on the O’Leary-Sant symptom score. There were no complications with the instillation. The authors said that liposomes offered potential improvement after one course of treatment for up to eight weeks. Large-scale, placebo-controlled studies are needed, of course, to show how well this treatment works, but it looks promising.

• Liposomes Beat DMSO, Elmiron for Easing Bladder Spasms in Animal Study

  Tyagi P, Hsieh VC, Yoshimura N, Kaufman J, Chancellor MB. Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for reducing bladder hyperactivity. BJU Int. 2009 Jul 7. [Epub ahead of print]

  Instilled liposomes eased bladder spasms better than DMSO or pentosan polysulfate (Elmiron) in this study of rats with irritated bladders. Six rats each got instillations of DMSO (50 percent), Elmiron (6 mg/mL), or liposomes (2 mg/mL) for two hours. The researchers measured the time between bladder contractions as well as bladder pressure, and the bladder pressure threshold for urination. The time between bladder contractions increased (fewer bladder spasms) significantly after instillation with Elmiron and liposomes, but not with DMSO. The improvement with liposomes (about 160 percent) was more than double that with Elmiron (about 60 percent). Liposomes did not affect the pressure threshold, Elmiron increased it slightly, and DMSO increased it greatly. DMSO also increased bladder pressure, whereas liposomes and Elmiron had no effect.

• Liposomes Hold Promise for No-injection Botox Treatment

  Chuang YC, Tyagi P, Huang CC, Yoshimura N, Wu M, Kaufman J, Chancellor MB. Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using liposomes. J Urol. 2009 Aug;182(2):786-92. Epub 2009 Jun 18.

  As a treatment used in IC patients, botulinum toxin A (Botox) is usually injected into the bladder wall. But liposomes with Botox in them may allow the medication to act where it’s needed without injection, indicates an animal study. Rats received instillations of liposomes alone, Botox alone, and liposomes encapsulating Botox and then received a potentially irritating substance in the bladder. The researchers measured the time between bladder contractions and also looked at molecular indicators of inflammation and nerve activity. Although all three bladder contractions significantly, the liposomes with Botox did not compromise the animals urinary function. They also have improvements in indicators of inflammation and nerve activity.

• Genistein, Suramin May Make IC Cells Act Normal

  Sun Y, Keay S, Lehrfeld TJ, Chai TC. Changes in Adenosine Triphosphate-stimulated ATP Release Suggest Association Between Cytokine and Purinergic Signaling in Bladder Urothelial Cells. Urology. 2009 Jul 21. [Epub ahead of print]

  Basic research related to antiproliferative factor (APF) shows that an older drug and an isoflavone found in soy have potential as effective instillations for IC. ATP has been found to play a role in transmitting pain signals in the bladder. Also, APF and the related epidermal growth factor (EGF) have negative effects on bladder lining cells. This research looked at a possible relationship -- how APF and EGF affect ATP-related cell signaling. Treating normal cells with EGF or APF increased ATP release and ATP receptors, turning the normal cells into IC cells. But when the researchers treated normal and IC bladder lining cells with genistein, which blocks EGF, release of ATP went down significantly and made IC cells act like normal ones. Suramin treatment of normal bladder cells exposed to the destructive APF significantly reduced ATP release. The apparent relationship between ATP-related cell signaling and cytokines should be explored further, said the investigators.

• Neurontin Helps in Severe Case, But Not by Itself

  Takatani J, Takeshima N, Okuda K, Miyakawa H, Noguchi T. A case of perineal pain related to interstitial cystitis which was supposed to be relieved with gabapentin. J Anesth. 2009;23(3):474-5. Epub 2009 Aug 14.

  Gabapentin (Neurontin) was helpful for a woman with IC and severe pain, but other treatments were needed, showed this case report by Japanese anesthesiologists. The 60-year-old woman, who had pain in the perineal and thigh area and frequent urination, went to six different clinics over 14 months before she got her IC diagnosis. Ineffective initial treatment included acetaminophen, a nonsteroidal anti-inflammatory drug, an SSRI antidepressant, and a muscle relaxant. The anesthesiologists gave her epidural lumbar nerve blocks with lidocaine four times a day, which helped greatly, but low blood pressure forced the doctors to end that treatment. She then got another nerve block in the hypogastric plexus with another medication. She kept taking Neurontin, which helped but needed to be increased. Ultimately, she was taking 900 mg/day. Because it did not help her frequency, she underwent hydrodistention. After that, her pain disappeared and her frequency returned to normal. (The article did not specify how long.) Neurontin was useful, but it was not the only therapy needed.

• Growth Factor Reveals Gender Differences, Points to Treatment

  Tyagi P, Tyagi V, Yoshimura N, Witteemer E, Barclay D, Loughran PA, Zamora R, Vodovotz Y. Gender-Based Reciprocal Expression of Transforming Growth Factor-Beta1 and the Inducible Nitric Oxide Synthase in a Rat Model of Cyclophosphamide-Induced Cystitis. J Inflamm (Lond). 2009 Aug 19;6(1):23. [Epub ahead of print]

  Because the cytokine transforming growth factor beta-1 (TGF-beta1) regulates nitric-oxide related inflammation, it might play a role in future IC diagnosis and treatment. In addition, male and female bladders produce different amounts of anti-inflammatory and prohealing TGF-beta1 in response to IC-like irritation, found these researchers. Nitric oxide (NO) is produced during inflammation and has been found in higher levels in IC patients’ urine. Researchers found that female rats produced much higher levels of NO reaction products than male rats, even without bladder irritation. The sexes had the same normal levels of TGF-beta1. After bladder irritation, male rats produced much lower levels of NO reaction products and higher levels of TGF-beta1 in urine than the female rats did. Overall, the more TGF-beta1 in the urine, the lower levels of the NO reaction products there were. TGF-beta1 and an NO-related protein were mostly found in the bladder lining. TGF-beta1 is known to be an anti-inflammatory and pro-healing modulator in the upper urinary tract (above the bladder), and these results imply it may also play a role like this in the lower urinary tract (bladder and below) and might lead to a helpful, healing treatment.

• Nerve Stimulation at Ankle as Good as Detrol LA for Frequency

  Peters KM, Macdiarmid SA, Wooldridge LS, Leong FC, Shobeiri SA, Rovner ES, Siegel SW, Tate SB, Jarnagin BK, Rosenblatt PL, Feagins BA. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009 Sep;182(3):1055-61. Epub 2009 Jul 18.

  For frequency, posterior tibial nerve stimulation (PTNS), which uses an acupuncture-like needle with electrical stimulation at the ankle, did just as well as a standard overactive bladder drug. This trial with 100 patients with frequency pitted 12 weekly tibial nerve stimulation treatments against 12 weeks of extended-release tolterodine (Detrol LA) 4 mg/day. When patients asked how they did overall, more who got stimulation said they were cured or improved than patients taking the drug. Doctors treating them thought they did about the same. The more objective measurements, such as voiding diaries and overactive bladder questionnaires, showed similar improvements in each group. Although focused on overactive bladder treatment, this trial shows the therapy may have potential in IC.

• Nerve Stimulation at Ankle Takes Down Chronic Prostatitis Symptoms, Pain

  Kabay S, Kabay SC, Yucel M, Ozden H. Efficiency of posterior tibial nerve stimulation in category IIIB chronic prostatitis/chronic pelvic pain: a Sham-Controlled Comparative Study. Urol Int. 2009;83(1):33-8. Epub 2009 Jul 27.

  A sham-controlled study showed posterior tibial nerve stimulation (PTNS), which uses an acupuncture-like needle with electrical stimulation at the ankle, can ease symptoms and pain for men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Because CP/CPPS and IC are thought to have similar pain mechanisms, the technique may have potential for IC pain as well. The study included 89 patients who had pelvic pain resistant to therapy; 45 got nerve stimulation, and 44 got sham treatment for 12 weeks. They filled out the NIH Chronic Prostatitis Symptom Index questionnaire and rated their pain and urgency on a 10-point scale. The investigators defined response as a drop of 50 percent or more on mean scores and partial response as a drop of 25 percent to 50 percent. At the end of treatment, pain responded to treatment in 40 percent (18 men) and partially responded in 60 percent (27), and symptoms responded to treatment in 67 percent (30) and partially responded in 33 percent (15). Mean symptom scores dropped from 23.6 at the beginning to 10.2, pain scores from 7.6 to 4.3, and urgency scores from 5.7 to 3.4. Scores for symptoms, urgency, and pain didn’t change at all for the men who got sham treatment.

• Visceral Pain Research Could Bring New Therapies Soon

  Sengupta JN. Visceral pain: the neurophysiological mechanism. Handb Exp Pharmacol. 2009;(194):31-74.

  Although this article mainly reviews potential mechanisms of chronic pain from internal organs, it holds out new hope for treatment. Because reports are emerging that various peptide molecules are involved in visceral pain, better therapy to manage it may be coming “relatively soon,” said the author.

• East Asian Urologists Develop IC Guidelines

  Homma Y, Ueda T, Tomoe H, Lin AT, Kuo HC, Lee MH, Lee JG, Kim DY, Lee KS; The interstitial cystitis guideline committee. Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome. Int J Urol. 2009 Jun 22. [Epub ahead of print]

  East Asian urologists have now developed guidelines for IC diagnosis and treatment based on the Japanese guidelines, published earlier this year. These guidelines define IC as a disease of the urinary bladder diagnosed by three requirements:

  • a characteristic complex of lower urinary tract symptoms
  • bladder pathology such as Hunner’s ulcer and bladder bleeding after hydrodistention
  • exclusion of confusable diseases

  The characteristic symptom complex, which they have termed “hypersensitive bladder syndrome” (HBS), is defined as bladder hypersensitivity, usually associated with urinary frequency, with or without bladder pain. The authors recommend HBS as a diagnosis when that is not confirmed by the other two requirements. Although many therapies are available, most lack a high level of evidence backing them up, leaving very few therapies to recommend. IC has a number of causes, with interaction nervous, immune and endocrine factors forming a vicious cycle, provoking and maintaining inflammatory reactions in the bladder, said the committee. The guidelines authors called for standardizing the criteria for including patients in clinical trials as well as for the methods for assessing treatment effectiveness to improve research for this disabling disease, which has proved to be more prevalent than previously believed. More information about the guidelines is posted in the Clinical Care section.

• Urologic Conditions Are Undertreated

  Hall SA, Link CL, Hu JC, Eggers PW, McKinlay JB. Drug treatment of urological symptoms: estimating the magnitude of unmet need in a community-based sample. BJU Int. 2009 Jun 22. [Epub ahead of print]

  Only a small proportion of people with urologic symptoms are getting recommended drug treatments, showed an analysis of the Boston Area Community Health (BACH) Survey. The survey included 5,503 men and women in the Boston area. The effort assessed urologic symptoms and also medication use in the past four weeks. Compared with the prevalence of symptoms, the prevalence of use of medications was very low among both men and women. The highest use was in men with moderate to mild lower urinary tract and benign prostatic hyperplasia (prostate enlargement) symptoms, but even among those men, only 9.6 percent used recommended drugs. Use of medications did not vary consistently by race and ethnicity or by socioeconomic status, but use was often related to how severe symptoms were. Although not everyone with symptoms needs drug treatment, the results suggest there is a substantial unmet need in the general population, said the authors.

• “Love Hormone” May Soothe Sensitive Bladders

  Black LV, Ness TJ, Robbins MT. Effects of Oxytocin and Prolactin on Stress-Induced Bladder Hypersensitivity in Female Rats. J Pain. 2009 Jul 10. [Epub ahead of print]

  Oxytocin, sometimes called the “love hormone,” seems to ease bladder hypersensitivity that’s related to stress. Because many mothers with IC have reported their bladder pain goes down during breastfeeding, the researchers tested the effects of oxytocin and prolactin, two hormones produced at that time. Similar to humans, lactating rats are less sensitive to bladder distention than female rats who are not lactating. Groups of female rats received either hormone or saline instilled into the lower body cavity after they were stressed with mild foot shocks. The bladders of the rats that got oxytocin before the stressful event showed much less bladder hyperactivity in response to bladder distention than those that got prolactin or saline. Prolactin actually made the bladder more sensitive in rats that hadn’t undergone the stress but had no effect on those that had the foot shocks. But oxytocin eased the response to bladder distention for the rats that hadn’t been stressed. The oxytocin-treated rats also behaved in a way that suggested they were less anxious. Systemic oxytocin might be a worthwhile treatment for patients whose chronic pain can be exacerbated by stress.

 

• Biofeedback, Estim Ease Symptoms

  Bendaña EE, Belarmino JM, Dinh JH, Cook CL, Murray BP, Feustel PJ, De EJ. Efficacy of transvaginal biofeedback and electrical stimulation in women with urinary urgency and frequency and associated pelvic floor muscle spasm. Urol Nurs. 2009 May-Jun;29(3):171-6.

  Transvaginal biofeedback and electrical stimulation may cut urinary symptoms by more than half. These nurses used the techniques in 52 women with urinary symptoms associated with pelvic floor muscle spasm. The women reported a mean symptom improvement of 64.5 percent.
  
  

• Results of Randomized Clinical Trial of PT on the Way

  Fitzgerald MP, Anderson RU, Potts J, Payne CK, Peters KM, Clemens JQ, Kotarinos R, Fraser L, Cosby A, Fortman C, Neville C, Badillo S, Odabachian L, Sanfield A, O’Dougherty B, Halle-Podell R, Cen L, Chuai S, Landis JR, Mickelberg K, Barrell T, Kusek JW, Nyberg LM; Urological Pelvic Pain Collaborative Research Network. Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for the Treatment of Urological Chronic Pelvic Pain Syndromes. J Urol. 2009 Jun 15. [Epub ahead of print]

  This research group is putting physical therapy (PT) through rigorous testing for the urological pelvic pain syndromes, IC and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), in the last of the clinical trials through the NIH-sponsored Urological Pelvic Pain Collaborative Research Network. The ICA covered the news about this trial in our reports from the 2008 American Urological Association (AUA) annual meeting. Now, the AUA’s official journal, the Journal of Urology, has published the result of the preliminary study, which pitted PT for the pelvic floor against general massage. Therapists were indeed able to adhere to a treatment protocol, essential for a valid study. The response rate was 57 percent for the targeted PT compared with 21 percent for general massage, a significant difference. We should be hearing about the final results of this trial at next year’s AUA meeting or possibly before then.

 

• New Treatments Not Ready for Prime Time, Say French Urologists

  Gamé X, Bart S, Castel-Lacanal E, De Sèze M, Karsenty G, Labat JJ, Rigaud J, Scheiber-Nogueira MC, Ruffion A; comité de neuro-urologie de l’Association française d’urologie. Alternative treatments for interstitial cystitis. Prog Urol. 2009 Jun;19(6):357-363. Epub 2009 May 5.

  After a look at various new therapies for IC, the French Association of Urology’s neurourology committee decided they’re not ready to be used routinely. Those treatments included posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, botulinum toxin injections into the bladder muscle, and surgery. The level of evidence so far is just too low, they said.

 

• Bladder Botox Gets Closer to Prime Time

  Silva CM, Cruz F. Has botulinum toxin therapy come of age: what do we know, what do we need to know, and should we use it? Curr Opin Urol. 2009 May 13. [Epub ahead of print]

  Botulinum toxin A (Botox) injection therapy for the bladder and prostate is getting closer to going prime time, although for IC, it’s still in the research arena, said these authors. The application that has the most evidence so far is neurogenic detrusor overactivity. This overactivity is the result of nerve or brain disease or damage, such as spinal cord injury. For other types of bladder overactivity, prostate enlargement, or IC, they believe its use should still be restricted to research centers in well-designed clinical trials. That Botox can be used today to avoid more invasive therapy, such as bladder augmentation surgery, for patients with hard-to-treat neurogenic bladder overactivity is a hopeful sign for people with IC.

 

• No Sexual Function Improvement from InterStim

  Ingber MS, Ibrahim IA, Killinger KA, Diokno AC, Peters KM. Neuromodulation and female sexual function: does treatment for refractory voiding symptoms have an added benefit? Int Urogynecol J Pelvic Floor Dysfunct. 2009 May 14. [Epub ahead of print]

  Sexual function scores didn’t improve in IC/painful bladder syndrome (PBS) patients after they got InterStim, showed this study that looked at sexual function in women who had overactive bladder or IC/PBS. Among the 105 women they studied, the researchers had 6-month data on sexual function for 54. Of those, only 27 were sexually active before their surgery and at the time they were followed up. Overactive bladder patients had more of an improvement than IC/PBS patients, but neither group had a statistically significant improvement.
  
  

• Electroacupunture Eases Pelvic Pain

  Lee SH, Lee BC. Electroacupuncture relieves pain in men with chronic prostatitis/chronic pelvic pain syndrome: three-arm randomized trial. Urology. 2009 May;73(5):1036-41.

  Electroacupuncture eased symptoms and pain significantly in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which may mean it has potential for IC patients, too. This Korean study was small but, nevertheless, controlled. The 39 men were randomly assigned to three different treatments. All got advice and were prescribed exercise. One group received advice and exercise alone, another had that plus electroacupuncture, and another had that plus sham acupuncture. After six weeks, symptom scores decreased significantly in the electroacupuncture group compared with the other ones, especially in pain-related symptoms. Levels of prostaglandin E2, which plays a role in inflammation, were significantly lower in the electroacupuncture group’s urine, whereas levels rose in the other groups.
  
  

• Sleep Improves when Symptoms Do

  Nickel JC, Payne CK, Forrest J, Parsons CL, Wan GJ, Xiao X. The relationship among symptoms, sleep disturbances and quality of life in patients with interstitial cystitis. J Urol. 2009 Jun;181(6):2555-61. Epub 2009 Apr 16.

  When symptom index scores improved, so did sleep and quality of life scores, found an analysis of a trial of pentosan polysulfate (Elmiron) for IC. The patients in the study not only completed the Interstitial Cystitis Symptom Index questionnaire but also an adapted Medical Outcomes Study Sleep scale and the Medical Outcomes Study Short Form-12 Health Survey during the trial. By week 32 of treatment, symptom scores as well as sleep scores improved, and the degree to which sleep improved correlated with how much symptoms improved. Those who responded to the treatment also showed significant improvement in their physical health as measured by the survey.
  
  

• New Approach Treats Hunner’s Ulcer Successfully with Steroid Injection

  Cox M, Klutke JJ, Klutke CG. Assessment of patient outcomes following submucosal injection of triamcinolone for treatment of Hunner’s ulcer subtype interstitial cystitis. Can J Urol. 2009 Apr;16(2):4536-40.

  When urologists treat IC patients’ Hunner’s ulcers directly through a cystoscope, they usually fulgurate them, that is, burn them off with electricity or a laser. But these urologists tried a different approach, injecting a corticosteroid into the ulcer just under the mucosal layer. With the patients under anesthesia, the doctors injected 10 mL of triamcinolone acetonide (40 mg/mL), 0.5 mL at a time, into the submucosal space at the center and periphery of 30 patients’ ulcers. The doctors had patients answer two questionnaires, the International Prostate Symptom Score (IPSS) and the Pelvic Pain and Urgency/Frequency (PUF) symptom scale, to assess the results and also asked patients to rate their overall impression of results right after surgery. The results were successful, with the average IPSS score dropping from 21 to 11, and the average PUF score from 20 to 11 at four weeks. Right after the operation, 21 patients (70 percent) said they were very much improved.
  
  

•  When Treatment Works, Sleep Improves

  Nickel JC, Payne CK, Forrest J, Parsons CL, Wan GJ, Xiao X. The Relationship Among Symptoms, Sleep Disturbances and Quality of Life in Patients With Interstitial Cystitis. J Urol. 2009 Apr 15. [Epub ahead of print]

  In a study of pentosan polysulfate (Elmiron), patients filled out questionnaires that allowed the researchers to see whether their sleep and quality of life improved -- in addition to their IC symptoms. The 128 patients took 300 mg of Elmiron per day and filled out questionnaires at the start of the study and 8, 16, 24, and 32 weeks later. The questionnaires included the Interstitial Cystitis Symptom Index, an adaptation of a standard sleep scale, and a standard 12-question health survey. At the beginning of the study, the relationship between sleep scores and the physical and mental components of the health survey were apparent. After 32 weeks, the 48 patients who responded to treatment had an average improvement in sleep score of about 12 points, whereas the 64 patients who didn’t respond to therapy improved by only about 2 points -- a significant difference. Sleep improvement correlated with how much symptoms improved. At the end of the study, the patients who did get help from the treatment had better scores on the physical component of the health survey than patients who didn’t get significant help from the treatment.
  
  

• Could Noninvasive Shock-Wave Treatment Hold Promise for IC?

  Zimmermann R, Cumpanas A, Miclea F, Janetschek G. Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome in Males: A Randomised, Double-Blind, Placebo-Controlled Study. Eur Urol. 2009 Mar 25. [Epub ahead of print]

  Extracorporeal shock-wave treatment (ESWT) is a noninvasive therapy that directs sound waves or “shock” waves to a problem area in the body. It’s usually used to treat kidney stones, breaking them up into tiny fragments that can be passed in the urine. But these urologists applied low sound waves to the perineum of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), using no anesthesia, and got very encouraging results. The randomized, double-blind (neither patients nor doctors knew who got the real treatment), placebo-controlled study included 60 men who had had CP/CPPS symptoms for at least three months. The men got the real or sham treatment once a week for four weeks. The effects on pain, quality of life, and voiding were all highly significant for the real treatment compared with the placebo. This treatment has the advantage of being easy, safe, and relatively inexpensive, with no side effects, and it can be repeated any time. Because CP/CPPS is similar to IC, we may hear about this treatment being tried in IC, too, in the future.
  
  

• New Instillation Combination Cuts Inflammation in the Lab

  Schulz A, Vestweber AM, Dressler D. Anti-inflammatory action of a hyaluronic acid-chondroitin sulfate preparation in an in vitro bladder model. [Article in German] Aktuelle Urol. 2009 Mar;40(2):109-12. Epub 2009 Mar 18.

  A combination of chondroitin sulfate and hyaluronic acid was studied in the laboratory for its effects on bladder lining cells. Chondroitin sulfate, commonly used in joint supplements, is the major active ingredient of the instillation solution Uracyst (not yet approved in the United States). Cystistat, also used for instillation, consists of a type of hyaluronic acid. These ingredients together were added to cultures of bladder lining cells, which were then exposed to TNF-alpha to prompt inflammation. To judge the degree of inflammation, the researchers measured levels of interleukin 6 (IL-6), a cytokine that these inflamed cells release. After the treatment, the level of IL-6 release went down, and the treatment did not adversely affect the cells, even in high concentrations. The researchers think this indicates that IC patients will tolerate the product well and that cell cultures are useful for screening new IC therapies.
  
  

• Urologists Give Guidance on Diagnosing, Treating IC in Kids

  Sea J, Teichman JM. Paediatric painful bladder syndrome/interstitial cystitis: diagnosis and treatment. Drugs. 2009;69(3):279-96.

  This article has done a great service by acknowledging that IC does indeed exist in children and adolescents and needs to be treated carefully. The authors reviewed the literature on the potential causes of IC, the disease process, tests, and treatment. Most of that work has been done in adults, and only a few studies have been published -- most of them long ago -- on IC in children. Some research indicates that about 25 percent of adults with IC had chronic urinary tract problems in childhood or IC symptoms in childhood that got more severe over time. The authors said that, in general, the same diagnostic procedures and treatments used in adults can be used in children, with certain exceptions and, of course, adjusted medication dosages. Those dosages are given in the article. They noted that potassium sensitivity testing not only has limitations in adults but can be difficult to perform and even sometimes cruel in children because of the pain it may cause. Diagnosis can be based mainly on the history and physical examinations, and voiding diaries are helpful. In addition to common adult symptoms, especially with food and beverage triggers, children may also have wetting.
  
  Similar to that for adults, treatment for children includes managing diet triggers and using standard medicines, such as pentosan polysulfate (Elmiron), amitriptyline (Elavil), hydroxyzine (Atarax, Vistaril), cimetidine (Tagamet), or instillations. The authors said that most physicians and parents would be reluctant to have children take amitriptyline and that low dosages may be helpful for adolescents. For instillation, most clinicians would likely prefer “therapeutic solution” (anesthetic combinations) over DMSO, citing “transient pain” as a side effect of DMSO. For some patients, however, the pain level may be high and the pain long lasting -- something to avoid in treating children. The authors noted that the only report of DMSO use in children was in a four-year-old who required additional instillation with something else, which was not specified.

 

• Multispecialty Panel Makes IC Diagnosis, Treatment Recommendations

  Forrest JB, Mishell DR Jr. Breaking the cycle of pain in interstitial cystitis/painful bladder syndrome: toward standardization of early diagnosis and treatment: consensus panel recommendations. J Reprod Med. 2009 Jan;54(1):3-14.

  Chronic pelvic pain, often the result of IC/painful bladder syndrome (PBS), affects about 15 percent of women in the United States. Even though IC/PBS is often the source, there are no guidelines for diagnosis and treatment, so it takes a long time for patients to get treated appropriately. That’s why a panel of providers in urology, gynecology, urogynecology, and general women’s health met to review the recent literature, reach consensus, and develop algorithms (step-by-step recommendations) for diagnosis and treatment. The group emphasized that diagnosis may not require every test available and can be based on a combination of things, including physical examination, questionnaires, cystoscopy, and potassium sensitivity testing. Potassium sensitivity testing, however is painful for those with damaged bladder linings, as in IC. The article mentions anesthetic instillation as a potential alternative. The authors emphasized that all sources of pain should be treated and that to achieve the best outcome, providers and patients should use many treatment strategies (multimodal therapy), including oral medications, bladder instillations, dietary modification, and psychological counseling. The primary goals are relief of pain and improvement in quality of life. The American Urological Association is also in the process of developing guidelines.
  
  

• Pudendal Neuralgia Called Real but Rare

  Stav K, Dwyer PL, Roberts L. Pudendal neuralgia. Fact or fiction? Obstet Gynecol Surv. 2009 Mar;64(3):190-9.

  This review article takes a look at the evidence so far for pudendal neuralgia (PN) or pain along the course of the pudendal nerve. The nerve and its branches serve the anal and genital areas. PN is sometimes misdiagnosed as IC, unexplained vulvodynia, endometriosis, unexplained testicular pain, chronic pelvic pain syndrome, or other pelvic disorders. Patients have often undergone many treatments that haven’t worked. Typically, they have pain in the areas the nerve serves, which may include not only the anal and genital regions but also the inner leg, buttocks, and abdomen. To help make the diagnosis, other conditions need to be ruled out. Typically, the pain is worse with sitting and is relieved with standing, lying down, or sitting on a donut cushion, toilet, or other seat that takes pressure off the nerve. Injection of nerve blocks to relieve the pain can help confirm the diagnosis. The authors said that commonly used neurophysiologic tests are not definitive. Treatments include avoiding the things that put pressure on the nerve and cause pain, physical therapy, pain medicines, nerve blocks, neuromodulation, or in severe cases, surgery to release the nerve. The authors indicated that this condition shouldn’t necessarily be considered the same thing as pudendal nerve entrapment. They concluded that the condition is rare, but since it is often mistaken for other pelvic conditions, it is hard to say how common it is.
  
  

• Botox Treatment Research Makes Progress

  Smith CP. Botulinum toxin in the treatment of OAB, BPH, and IC. Toxicon. 2009 Mar 4. [Epub ahead of print]

  Research on botulinum toxin, especially type A (Botox), is ongoing in IC, overactive bladder (OAB), and benign prostatic hyperplasia (BPH) in men. In IC, evidence so far comes only from small series of cases. But today, for OAB and IC, treatment research is already in phase 2 and 3 clinical trials. (Phase 3 is the final stage.) Regulators in both the United States and the European Union are evaluating the treatments.
  
  

• Botox Finding a Place in Vulvodynia, Pelvic Floor Therapy

  Abbott J. Gynecological indications for the use of botulinum toxin in women with chronic pelvic pain. Toxicon. 2009 Mar 3. [Epub ahead of print]

  Injecting botulinum toxins (usually botulinum toxin A or Botox) is being tried and studied in pelvic pain conditions that are often though of as gynecologic, most notably provoked vestibulodynia (also called vulvar vestibulitis) and pelvic floor spasm. Patients with these conditions commonly report painful intercourse, painful bowel movements, and pain with menstrual periods. Based on the limited literature, injecting 20 to 40 U of Botox in the vulva may help for three to six months in women with provoked vestibulodynia. Retreatment seems to be successful and side effects limited. Studies of Botox injection for pelvic floor muscle spasm have included more patients, and a double-blind, randomized, controlled study -- the gold standard for evaluating effectiveness -- reported significant reductions in pelvic floor pressures and some types of pain. There was no significant difference, however, between the results of injection therapy and physical therapy. The authors suggest that physical therapy may be appropriate as a first-line treatment, with Botox injections reserved for cases when that’s not successful. These therapies have few side effects and look very promising, but more research needs to be done, said the authors.
  
  

• Research Group Developing Gene Therapy for IC Pain

  Goins WF, Goss JR, Chancellor MB, de Groat WC, Glorioso JC, Yoshimura N. Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain. Gene Ther. 2009 Feb 26. [Epub ahead of print]

  This abstract explains this research group’s rationale for their IC gene therapy research, which is progressing. No matter what the cause of IC, it is painful, involving increased or abnormal pain signals. Standard therapies are often just palliative, IC pain is hard to treat, and standard pain therapies all have drawbacks. But this treatment the group is working on has the potential to alleviate pain effectively. It involves using a modified simplex virus to deliver pain-killing proteins directly to the bladder.
  
  

• Receptors Are There for Potential New Cannabinoid Bladder Drugs

  Tyagi V, Philips BJ, Su R, Smaldone MC, Erickson VL, Chancellor MB, Yoshimura N, Tyagi P. Differential Expression of Functional Cannabinoid Receptors in Human Bladder Detrusor and Urothelium. J Urol. 2009 Feb 21. [Epub ahead of print]

  Researchers are already looking at cannabinoid (marijuana-related) drugs to soothe IC bladders, but until now, no one was entirely sure that the receptors were there for the drugs to act on. But this study found that the two major types of cannabinoid receptors are indeed in the bladder lining and in the bladder muscle (detrusor), with somewhat more found in the bladder lining. That suggests, said that authors, that these receptors do play a role in the bladder and that they can serve as a target for drugs acting on symptoms of IC/painful bladder syndrome (PBS).
  
  

• Botox Injections in the Pelvic Floor Can Ease Hard-to-Treat Pelvic Pain

  Abbott J, Med Hons B. The Use of Botulinum Toxin in the Pelvic Floor for Women with Chronic Pelvic Pain-A New Answer to Old Problems? J Minim Invasive Gynecol. 2009 Jan 21. [Epub ahead of print]

  Botulinum toxin (Botox) injections into the pelvic floor as a treatment to relieve pelvic floor muscle spasm and pain is a treatment that is still in its infancy, but early research suggests it may have an important role for women whose pelvic pain doesn’t yield to currently available treatment, said these authors. They noted that the few studies that have been done of the injections for provoked vestibulodynia (pain prompted by touch at the vaginal opening) show that these injections may be helpful in the short term -- three to six months -- and that retreatment seems to be successful, and the side effects are few. For pelvic floor muscle pain and tenderness, there is currently only one double-blind, randomized, controlled study. That study showed significant reduction in pelvic floor pressures with significant pain reduction for some types of pelvic pain. Physical therapy should be used as a noninvasive, first-line treatment, with Botox injections reserved for those who are not helped. The authors urged physicians to consider pelvic floor disorders as a cause of chronic pelvic pain in women and to diagnose and treat them as routine practice.

 

• Survey Shows Which Treatments Help

  Hill JR, Isom-Batz G, Panagopoulos G, Zakariasen K, Kavaler E. Patient perceived outcomes of treatments used for interstitial cystitis. Urology. 2008 Jan;71(1):62-6.

  With an internet survey, these researchers compared 750 patients’ assessments of how they fared after treatment with invasive procedures and treatment with medications. The invasive procedures included hydrodistention (62 percent), bladder instillation (40 percent), and urethral dilatation (26 percent). Six months later, 24 to 45 percent of patients said they were improved by these procedures, whereas 27 to 50 percent felt no effect and 26 to 31 percent got worse. The procedures with the best results for the largest share of patients were bladder instillation, which patients found to be beneficial 45 percent of the time, and sacral neuromodulation, which patients found helpful 56 percent of the time. A small number of patients had Hunner’s lesions and underwent cauterization or removal of the lesions. Of those, 55 percent said they were better. For all medical therapies, more patients said they were better than worse, and most patients said medications made them perceptibly better. Of patients who tried each medication, 53 percent said Elmiron made them feel better, 47 percent said amitriptyline (Elavil) did, 61 percent said Prelief did, 60 percent said Pyridium did, and 63 percent said codeine did. The medications that helped least were the anticholinergic (overactive bladder) drugs, which helped from 23 to 32 percent, and diphenhydramine (Benadryl), which helped 23 percent.
  
  

• Advances, Setbacks Characterize Vanilloid Drug Research

  Wong GY, Gavva NR. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks. Brain Res Rev. 2008 Dec 25. [Epub ahead of print]

  The vanilloid receptor TRPV1, known popularly as the "hot pepper" receptor, is a target that researchers, including IC researchers, have long aimed at for pain reduction. The receptor abundantly expressed in c-fibers, which are nerve fibers that sense pain. Substances that excite the receptor, such as capsaicin and resiniferatoxin, and substances that block the receptor have both been shown to reduce pain in experimental animals. Human trials have been done with these compounds in IC, shingles, osteoarthritis, bunionectomy, and Morton's neuroma. Trials of resiniferatoxin for IC did not work out, but new TRPV1-related drugs, including the blockers SB-705498 and AMG 517, are being tried in other conditions, which may ultimately help in IC. This review article summarizes the recent advances and setbacks of these compounds in drug development and predicts future directions.
  
  

• Vanilloid Receptor Plays Role in Chronic Pain and Chronic Cough

  Adcock JJ. TRPV1 receptors in sensitisation of cough and pain reflexes. Pulm Pharmacol Ther. 2008 Dec 27. [Epub ahead of print]

  The vanilloid receptor (TRPV1) may play a role in many types of pain-inflammatory, visceral, cancer, and neuropathic)-but also in inflammatory bowel disease (IBD), interstitial cystitis, urinary incontinence, pancreatitis, migraine, and airway disease (including chronic cough). TRPV1 is a member of a distinct subgroup of the transient receptor potential (TRP) family of ion channels. The receptor can be activated, not only by capsaicin (the hot pepper chemical) but also by other stimuli and chemicals. Substances that mediate inflammation and have been focuses of IC research, such as adenosine triphosphate (ATP), bradykinin, nerve growth factor (NGF), and prostaglandin E2 (PGE2), may activate vanilloid receptors indirectly. Also, after they are activated by one thing, these receptors seem to be sensitized to further activation by other things. That may be the key to why substances that aren't normally harmful can activate this receptor and cause either pain or cough. The receptor may be a great target, not only for pain drugs, but also for drugs to ease cough and airway problems.
  
  

• Bladder Injections of Botox Work Better than BCG

  El-Bahnasy AE, Farahat YA, El-Bendary M, Taha MR, El-Damhogy M, Mourad S. A Randomized Controlled Trial of Bacillus Calmette-Guerin and Botulinum Toxin-A for the Treatment of Refractory Interstitial Cystitis. UIJ. 2008 Dec;1(5).

  These Egyptian researchers pitted instillation of bacille Calmette-Guérin (BCG) against injections of botulinum toxin A (Botox) in a trial with 36 patients. These patients met the old from of the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) research definition of IC, which generally includes patients with more serious disease. One group of patients got 6 weeks of BCG therapy, the other got injections in the bladder of 300 units of Botox. Patients filled out questionnaires and voiding diaries. Eleven of the 16 patients who got BCG had an "excellent" overall response during the 23 weeks of follow-up, indicating a 71 percent improvement in a global rating, a 31 percent decrease in daily voids, a 54 percent decrease in nocturia, an 81 percent decrease in pelvic pain, a 71 percent decrease in urgency, and an 82 percent decrease in painful urination. Fourteen of the 16 patients who got Botox injections had an "excellent response" over 22 weeks, indicating a 92 percent overall improvement, a 68 percent reduction in daily voids, a 100 percent improvement tin nocturia, a 96 percent decrease in pelvic pain, a 100 percent decrease in urgency, and a 92 percent decrease in painful urination. These improvements were significantly better statistically than for patients who got BCG. These results for BCG therapy are very different from those of a randomized, controlled NIDDK-sponsored trial in the United States, which did not find BCG instillations to be better than placebo.
  
  

• Patients Generally Satisfied with Bladder Enlargement

  Astroza Eulufi G, Velasco PA, Walton A, Guzmán KS. Enterocystoplasty for interstitial cystitis. Deferred results. [Article in Spanish] Actas Urol Esp. 2008 Nov-Dec;32(10):1019-23.

  At a hospital in Chile, 15 IC patients with very bad IC underwent bladder enlargement surgery between 1999 and 2006. Before surgery, patients had a mean bladder capacity of 126 mL and had a mean frequency of 30.5 times a day. After surgery, their mean bladder capacity almost tripled to 355 mL, and their mean frequency went down to 8.3 times a day. Five patients had surgery-related complications. Thirteen patients were satisfied with the results in terms of frequency and 11 in terms of suprapubic pain.
  
  

•  Alkalinized Lidocaine Instillation Gives Sustained Relief

  Nickel JC, Moldwin R, Lee S, Davis EL, Henry RA, Wyllie MG. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int. 2008 Nov 13. [Epub ahead of print]

  Five days of instillations with a proprietary alkalinized lidocaine, PSD597, produced moderate to marked improvement in 30 percent of patients. That compared with about 10 percent in those who got placebo in this controlled, randomized, multicenter study of 102 IC/PBS patients. In addition the effects lasted beyond the treatment period. The peak levels of lidocaine in the patients' bloodstream were well below the toxic level. Although the authors called for long-term studies, they said this preliminary one showed that instillations can ease symptoms beyond the treatment period and that it is safe, well tolerated, and has none of the systemic side-effects patients often experience with oral drugs. This study, now published in a medical journal, is one that the ICA covered in its reports from the American Urological Association Meeting last May and in the ICA Update.
  
  

• CystoProtek Supplement Helps Severe IC in Uncontrolled Test

  Theoharides TC, Kempuraj D, Vakali S, Sant GR. Treatment of refractory interstitial cystitis/painful bladder syndrome with CystoProtek-an oral multi-agent natural supplement. Can J Urol. 2008 Dec;15(6):4410-4.

  This uncontrolled study tested the IC supplement CystoProtek, which contains glucosamine, chondroitin, hyaluronate, quercetin, and rutin, in 252 IC/PBS patients (25 men and 227 women) who hadn't had success with other treatments. The glucosamine, chondroitin, and hyaluronate are aimed at helping replace the glycosaminoglycan (GAG) layer that coats the bladder lining, and the quercetin and rutin are aimed at reducing bladder inflammation. Patients rated their symptoms before and after treatment on a scale of 1 to 10 at various times. Men had an average score of 7.5 at the beginning, which fell 52 percent to 3.9 after about a year, which was statistically significant. The women were divided into two groups, those with more severe and less severe IC. At the beginning of the study, those with more severe IC had an average score of 7.9, which fell 52 percent to 3.8 after an average of 11 months, a statistically significant difference. Those with less severe IC had their scores fall about 44 percent from 3.2 to 1.6 after an average of 10 months, which was also statistically significant, only less so. When the results for the women were evaluated based on the severity and length of time they had undergone treatment, the improvement was significant for the group with more severe symptoms. The authors called for prospective, randomized trials of this and similar supplements in patients who have not had other treatments work and in patients who have not yet had any treatment.
  
  

• Botulinum Toxin Shows Potential in Chronic Pain

  Jabbari B. Botulinum neurotoxins in the treatment of refractory pain. Nat Clin Pract Neurol. 2008 Dec;4(12):676-85.

  Pain that is hard to control with most pain medications is a challenge, but one that botulinum toxins might help meet. They have shown potential in reducing pain in IC and other conditions, and this article takes a look at why. Animal studies show that the toxins inhibit the release of pain peptides from nerve endings and sensory nerve bundles, that the toxins have anti-inflammatory and antiglutamate effects, which may protect nerves, reduce activity of sympathetic nerves (which regulate organ function), and inhibit discharge of sensory receptors in muscle. Long-term studies of botulinum toxin treatments in painful neck spasm (cervical dystonia) and low back pain show that the toxins' effects last after repeat injections, a sign that the treatment may help thwart the self-perpetuating nature of chronic pain.
  
  

• Oxazepam May Cut Nighttime Bathroom Trips

  Kaye M. Nocturia: a blinded, randomized, parallel placebo-controlled self-study of the effect of 5 different sedatives and analgesics. Can Urol Assoc J. 2008 Dec;2(6):604-8.

  This retired professor of medicine tested a number of medications on himself in a controlled way to see what their effects were on nighttime bathroom trips (nocturia). The medications included the sedatives oxazepam (Serax, a benzodiazepine related to diazepam or Valium), zopiclone (Imovane, not available in the United States, related to eszopiclone or Lunesta), and trazodone (Desyrel, an antidepressant often used for sleep) and the analgesics naproxen (Naprosyn, Aleve, a nonsteroidal anti-inflammatory agent) and oxycodone (as in OxyContin and combinations). In a previous study, he found that oxazepam decreased nocturia. In this study, the only drugs that reduced the nocturia significantly were naproxen and oxazepam. Oxazepam didn't change the volume of urine. Naproxen did by reducing water, salt, and potassium excretion. Even though sleep quality improved with zopiclone and pain relief improved with oxycodone, these drugs had no effect on nocturia. Oxazepam, he concluded, probably worked by making the bladder less irritable in a way that cannot be attributed to its sedative or pain killing effects or any decrease in urine or urine composition. The effect might come from gamma-aminobutyric acid (GABA) effects in the spinal cord or brain. The professor doesn't have IC, but these results might help guide research and treatment for IC patients with nocturia and sleep loss.
  
  

• Physical Therapy, Electrical Stimulation Eases Vulvodynia Pain

  Dionisi B, Anglana F, Inghirami P, Lippa P, Senatori R. Use of transcutaneous electrical stimulation and biofeedback for the treatment of vulvodynia (vulvar vestibular syndrome): result of 3 years of experience. Minerva Ginecol. 2008 Dec;60(6):485-491.

  Providers treated 145 women with vulvodynia using 10 weekly treatments of biofeedback, transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES) and having the patients practice stretching exercises for the pelvic floor at home. Vulvar pain improved for 76 percent of the women.
  
  

• Mechanisms of Chemokines in IC

  Sakthivel SK, Singh UP, Singh S, Taub DD, Novakovic KR, Lillard JW Jr. CXCL10 blockade protects mice from cyclophosphamide-induced cystitis. Immune Based Ther Vaccines. 2008 Oct 28;6(1):6. [Epub ahead of print]

  CXCR3 is a receptor for certain family of chemokines that are proinflammatory immune-system molecules. The receptor is usually found on certain types of white blood cells involved in inflammation. Levels of complexes with this receptor were high in IC patients' serum. In mice with a kind of cystitis, the levels of CXCR3 chemokines and other chemokines were also high, similar to that of IC patients. Messenger RNA for this and related chemokines were high on white blood cells in the bladder, and transcripts for other CXR3 chemokines were high in white cells in the lymph nodes in the groin. The numbers of certain inflammatory white blood cells and mast cells were high in the spleen, bladder, and lymph nodes. Blocking the most common chemokine that binds with CXCR3, known as CXCL10, damped down these reactions in the mice. CXCL10 is also known to be involved in sensory nerve signaling. This study, said the authors, is among the first to demonstrate some of the cellular and molecular mechanisms of chemokines in cystitis and may provide a new drug target for this disease.
  
  

• Gene Therapy for IC Bladder Pain Gets One Step Closer

  Yokoyama H, Sasaki K, Franks ME, Goins WF, Goss JR, Degroat WC, Glorioso J, Chancellor MB, Yoshimura N. Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. Hum Gene Ther. 2008 Oct 15. [Epub ahead of print]

  We reported on this University of Pittsburgh group's gene therapy work presented at the American Urological Association meeting last May. Now, their research on potential gene therapy for IC bladder pain has been published. They used a herpes virus vector to carry a gene for a precursor of enkephalin, one of the body's own natural opioid painkillers, into rats' bladder cells. When the rats had bladder irritation, those who got the gene had lower bladder hyperactivity and showed less pain-related behavior than the animals that got an unrelated gene. Laboratory analysis showed that the gene had been incorporated into the bladder and also the nerve roots that receive impulses from the bladder. The treatment didn't affect the animals' ability to urinate normally. This team is looking at this as a potential treatment for IC.
  
  

• Body Mechanics System Helps Ease Pelvic Pain

  Haugstad GK, Haugstad TS, Kirste UM, Leganger S, Wojniusz S, Klemmetsen I, Malt UF. Continuing improvement of chronic pelvic pain in women after short-term Mensendieck somatocognitive therapy: results of a 1-year follow-up study. Am J Obstet Gynecol. 2008 Oct 7. [Epub ahead of print]

  The Mensendieck system is a kind of physical therapy that emphasizes correcting posture, movement, and respiration patterns. It is popular in Europe, especially in Scandinavia, where this study was done. Forty women who had unexplained chronic pelvic pain were assigned to two groups: standard gynecologic treatment and gynecologic treatment plus Mensendieck somatocognitive therapy. They completed questionnaires that assessed psychological distress and general well-being and rated their pain before treatment, after 90 days of treatment, and one year later. Patients who got standard therapy did not improve significantly at one year. By contrast, those who got the additional Mensendieck therapy had their scores improve for all motor functions and pain, as well scores for coping, and anxiety-insomnia-distress. The investigators concluded that adding this therapy to standard care improves psychological distress, pain experience, and motor functions. In their abstract, the authors did not state whether they evaluated patients for interstitial cystitis.
  
  

• Botox for IC Still Needs Evidence

  Apostolidis A, Dasgupta P, Denys P, Elneil S, Fowler CJ, Giannantoni A, Karsenty G, Schulte-Baukloh H, Schurch B, Wyndaele JJ. Recommendations on the Use of Botulinum Toxin in the Treatment of Lower Urinary Tract Disorders and Pelvic Floor Dysfunctions: A European Consensus Report. Eur Urol. 2008 Sep 17. [Epub ahead of print]

  This report of a European expert panel consensus conference concluded that, so far, the evidence is inconclusive for recommending botulinum toxins for IC (which they called bladder pain syndrome), prostate diseases, and pelvic floor disorders. The panel recommended larger placebo-controlled and comparative trials to evaluate the therapies and their safety for treating lower urinary tract and pelvic floor disorders. The evidence for use of the type A toxin (Botox) is promising, and the treatment is recommended for intractable symptoms of neurogenic detrusor overactivity, the type of bladder overactivity that can be seen in spinal cord injury or spina bifida, for example.
  
  

• Urinary Tract Destruction Calls for Cautious Use of Painkiller

  Chu PS, Ma WK, Wong SC, Chu RW, Cheng CH, Wong S, Tse JM, Lau FL, Yiu MK, Man CW. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int. 2008 Aug 1. [Epub ahead of print]

  This article by urologists in Hong Kong reports on the destructive effect of ketamine abuse on the urinary tract. Abusers have some of the same symptoms as IC, but others as well. Inflammation of the bladder lining, a contract bladder, frequency, and urgency were among the symptoms. Many patients also had blood in the urine, reflux of urine from the bladder, and fluid enlargement of the kidney. Although it doesn't address the effects of temporary, low dose, and legitimate use of this painkiller, this article does sound a note of caution on the use of this painkiller in IC patients. The process in abusers may hold some clues to the process in IC, but the parallels emphasize how serious and physiologically destructive IC is in severe cases.
  
  

• Unmet Needs Great in Pain Management

  McCarberg BH, Nicholson BD, Todd KH, Palmer T, Penles L. The impact of pain on quality of life and the unmet needs of pain management: results from pain sufferers and physicians participating in an Internet survey. Am J Ther. 2008 Jul-Aug;15(4):312-20.

  This extensive survey and its analysis showed that, despite pain's high prevalence, many patients suffer with unrelieved or undertreated pain and that it has a huge impact on daily activities and quality of life for most sufferers. This team surveyed both pain sufferers and physicians. Of the 22,018 nonphysicians who responded to e-mail invitations, 606 met the survey's criteria as pain sufferers. Of these, 359 had moderate to moderately severe chronic pain and 247 had moderate to moderately severe acute pain. Physicians who responded included 241 specialists (orthopedic or general surgeons, pain specialists, or anesthesiologists), 125 primary care doctors, and 126 emergency medicine physicians. Many chronic pain sufferers reported that pain had deleterious effects on their mental health, employment status, sleep, and personal relationships. Most physicians did recognize the impact of pain on patient quality of life and that there were unmet needs in pain management, including inadequate pain control, end-of-dose pain, and side effects associated with increased dosing, which influenced their choice of pain medication. The authors encouraged effective communication between physicians and patients to not only improve overall pain management but also to establish shared treatment goals.
  
  

• Effectiveness of RTX Still Not Known

  Mourtzoukou EG, Iavazzo C, Falagas ME. Resiniferatoxin in the treatment of interstitial cystitis: a systematic review. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Jun 19. [Epub ahead of print]

  Studies on resiniferatoxin (RTX) treatment for IC show conflicting results. Of the six published studies, the largest study showed no improvement of overall symptoms after one treatment. Smaller studies of one RTX treatment gave conflicting results. Two studies that looked at multiple or prolonged treatment yielded more encouraging results. The effectiveness of the therapy remains unknown.
  
  

• New Target for IC, Overactive Bladder Drug Therapy Shows Potential

  Su X, Leon LA, Wu CW, Morrow DM, Jaworski JP, Hieble JP, Lashinger ES, Jin J, Edwards RM, Laping NJ. Modulation of Bladder Function by Prostaglandin EP3 Receptors In the Central Nervous System. Am J Physiol Renal Physiol. 2008 Jul 16. [Epub ahead of print]

  Researchers at GlaxoSmithKline are focusing on another receptor that may be a target for overactive bladder or IC drugs, the prostaglandin EP3 receptor in the central nervous system. These receptors, when triggered, may excite bladder activity. They administered two EP3 blockers, called DG041 and CM9, in both the abdominal cavity and the brain in experimental animals to assess the reaction of the bladder to being distended. Both compounds showed high affinity for the receptors, and both blocked the cellular activity induced by a compound that excites that receptor. The compounds administered both ways reduced the frequency of bladder contractions but not their strength, but administering the compounds in the body cavity produced strong, long-lasting effects, whereas administration in the brain produced only transient effects. That means, said the investigators, that these EP3 receptors are involved in urination at spinal and supraspinal centers and in sensation of bladder pain at the spinal cord level. Some EP3 receptor blocker may help control bladder overactivity and pain, they concluded.
  
  

• Researchers Look at Drug Target for Pain Hypersensitivity, Bladder Pain

  Robbins MT, Ness TJ. Footshock-Induced Urinary Bladder Hypersensitivity: Role of Spinal Corticotropin-Releasing Factor Receptors. J Pain. 2008 Jul 15. [Epub ahead of print]

  Receptors for corticotropin-releasing factor (CRF) might be a good target for drugs to ease bladder pain. Because hypersensitivity to pain is thought to play a role in bladder pain and because it is known to be brought on by stress, the investigators looked at ways to block that response in stressed rats. When stressed (by footshock), the rats’ bladders became hypersensitive. The researchers found that blocking the CRF(2) receptor, but not the CRF (1) receptor calmed the response to bladder distention. They administered a CRF(2)-like compound, urocortin 2, to the spine, which increased the response in a way that was similar to stress. The effect was significantly calmed by pretreating the animals with spinal aSVG30, a CRF(2) receptor blocker. Neither CRF nor the CRF(1) receptor blocker antalarmin had any effect on the bladder responses. The study supports the role of stress in making bladder pain worse and also implicates spinal urocortins and their receptor, CRF(2), as players in this process. This could ultimately lead to more effective treatments for IC pain as well as chronic pain that is worsened by stress, said the investigators.
  
  

• ATP Receptor Is Also Target for Bladder Pain Drug Development

  Brederson JD, Jarvis MF. Homomeric and heteromeric P2X3 receptors in peripheral sensory neurons. Curr Opin Investig Drugs. 2008 Jul;9(7):716-25.

  These neuroscience researchers at Abbott Laboratories detail what is known about the receptors for ATP and their role in pain, especially bladder pain. One of them, the P2X3 receptor, is very common in the bladder, which is rich in neurons containing this receptor. When ATP or similar compounds attach to the receptor, nerves are more sensitive to noxious stimulation. In animal research, blocking this receptor fully blocked certain types of chronic inflammatory and neuropathic pain. This receptor will be an important target for drugs for chronic pain including bladder pain.
  
  

• Osteopathic Technique Eases Pelvic Pain

  Grimaldi M. Painful perineum in all its forms. Contribution of manual medicine and osteopathy. Clinical study. [Article in French] J Gynecol Obstet Biol Reprod (Paris). 2008 Jul 7. [Epub ahead of print]

  This osteopathic gynecologist and colleagues used “manual medicine” to help treat pelvic pain, such as painful intercourse, vulvodynia, and coccygodynia, which, the author said, can be brought on by a bone and myofascial disorder. Six patients at this center and 86 others at other centers worldwide were treated, with 71 having satisfactory results after two sessions. The encouraging results to be confirmed on a larger scale to establish an appropriate teaching protocol, noted the author.
  
  

•  When Elmiron Controls Symptoms, Patients Are Satisfied with Treatment

  Sand PK, Kaufman DM, Evans RJ, Zhang HF, Fisher DL, Nickel JC. Association between response to pentosan polysulfate sodium therapy for interstitial cystitis and patient questionnaire-based treatment satisfaction. Curr Med Res Opin. 2008 Jun 25. [Epub ahead of print]

  This study showed that patients who got good symptom control (a reduction of 30 percent or more) with pentosan polysulfate (Elmiron) were more satisfied with their treatment.
  
  

• Newly Discovered Receptor Shows Potential as Bladder Pain Target

  Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X. AMTB, a TRPM8 Channel Blocker: Evidence in Rats for Activity in Overactive Bladder and Painful Bladder Syndrome. Am J Physiol Renal Physiol. 2008 Jun 18. [Epub ahead of print]

  Earlier this year, Japanese researchers discovered that a single receptor TRPM8, is likely responsible for all cold sensation. That shows potential for activating the pain reducing properties of cold and also blocking pain sensations (which can be like those resulting from extreme cold). Now, investigators at GlaxoSmithKline are studying the receptor’s potential as a drug target for overactive bladder and bladder pain. They used a blocker, known as AMTB, of the TRPM8 channel to see if it changed the animals’ reactions to bladder filling and found that it did reduce both voiding reflexes and pain reflexes.
  
  

• Drug Therapy for Chronic Pain Outlined

  Lynch ME. The pharmacotherapy of chronic pain. Rheum Dis Clin North Am. 2008 May;34(2):369-85.

  In this article, these Canadian pain management specialists outline what they believe the best evidence supports as the approach to chronic pain. (This is aimed mainly at rheumatic diseases, which include fibromyalgia.) The usual approach is to start with a nonopioid painkiller for mild to moderate pain. If this is inadequate or patients don't tolerate it well and if sleep loss is also a concern, then it is reasonable to add an antidepressant with painkilling qualities. If there is a component of nerve pain or fibromyalgia, then they suggest trying one of the gabapentinoids, such as gabapentin (Neurontin) or pregabalin (Lyrica). When that approach is inadequate, then they suggest adding an opioid analgesic. But for moderate to severe pain, they would start a trial of a chronic opioid earlier. Cannabinoids and topicals may also be appropriate as single agents or in combination, they said.
  
  

• GAG Replacer Instillation Helps Increase Bladder Capacity

  Daha LK, Riedl CR, Lazar D, Simak R, Pfluger H. Effect of intravesical glycosaminoglycan substitution therapy on bladder pain syndrome/interstitial cystitis, bladder capacity and potassium sensitivity. Scand J Urol Nephrol. 2008 Jan 8:1-4. [Epub ahead of print]

  At this Austrian clinic, urologists gave 27 patients GAG-replacing instillations weekly for 10 weeks. They used a modified potassium sensitivity test after instillation of the therapy to help assess response. In the 13 patients who did respond, maximum bladder capacity doubled with potassium instillation compared with their previous response to it. Their capacity in response to saline instillation increased 17 percent. The others had their capacity decrease by 35 percent with a saline solution and experienced no change in response to the potassium solution.
  
  

• Drug Development Programs Take Aim at “Hot Pepper” Receptor

  Messeguer A, Planells-Cases R, Ferrer-Montiel A. Physiology and pharmacology of the vanilloid receptor. Curr Neuropharmacol. 2006 Jan;4(1):1-15.

  This article reviews research on vanilloid receptor 1, the “hot pepper receptor,” and discusses the great potential for drugs that target it. Interestingly, this receptor is made very active by inflammatory agents, which is thought to be part of the process of sensitizing pain receptors leading to oversensitivity to heat. The research is building a strong case that this receptor is involved in both outer-body and internal organ inflammatory pain, such as inflammatory bowel disease, bladder inflammation, and cancer pain. Drug development programs aimed at this receptor are intensive. The challenge will be to develop receptor blockers that correct overactivity while still allowing normal pain and sensation, said the authors.

Revised May 31, 2013