AUA 2008


AUA Meeting Shows What Works, Brings Recognition

May 17-22, 2008, Orlando, FL
The 2008 American Urological Association Annual Meeting in Orlando, Florida, brought lots of good news for people with IC. Potential treatments are always being discussed, but now, good science is showing what works—and is surprising many urologists. And the good news isn’t just about science and treatments. It’s also about recognition.

IC and pelvic pain in women were the subject of a “state-of-the-art” lecture at a plenary session by a highly-respected urologist whose major focus is not IC research. In addition, IC experts taught three different courses for their colleagues on IC. That shows that IC diagnosis and treatment has become an important part of urology practice in general and that every urologist needs more good information about IC.

This information can also be found in the Fall 2008 ICA Update with a reader-friendly summary of every study relevant to IC presented at the meeting.

TREATMENT

DIAGNOSIS / ASSESSMENT

EPIDEMIOLOGY

SOCIAL ISSUES

BASIC RESEARCH

TREATMENT

Science Now Backs Up Value of Pelvic Floor Physical Therapy

Randomized multicenter pilot trial shows benefit of manual physical therapies in the treatment of chronic pelvic pain

MP Fitzgerald, Chicago, IL, RU Anderson, CK Payne, Stanford, CA, J Potts, Cleveland, OH, KM Peters, Royal Oak, MI, JQ Clemens, Ann Arbor, MI, L Cen, S Chuai, JR Landis, Philadelphia, PA

Pelvic floor directed physical therapy for IC symptoms has become increasingly popular, but it hasn’t had the scientific backing that placebo-controlled clinical trials can give a therapy. Whether the benefits came from the techniques or just the personal attention and touch were open questions for many. But this trial did help answer those questions, even though it wasn’t designed to do so. It was designed to show whether such a trial could be done. Because a sham therapy didn’t seem possible, the investigators compared the effects of physical therapy against general, whole-body, Western-style massage. The physical therapy included connective tissue manipulation of external tissues of the lower limbs, buttocks, and abdominal wall and trigger-point treatments of the abdominal wall and pelvic floor. The investigators showed a larger trial was feasible because they were able to standardize the physical therapy treatment and massage, doctors correctly identified pelvic floor problems, and patients were willing to be randomized to one treatment or the other and follow through. Forty-seven patients (23 men and 24 women) were randomized to one treatment or the other at 6 participating centers, and 44 completed the study. Patients got weekly treatments of one hour for a median of 10 weeks. The major measure (within 2 weeks of the end of therapy) of success was moderate or marked improvement on a global response assessment (which asks patients whether they are better, the same, or worse and how much). Overall, 57% of patients responded to physical therapy compared with 21% to general massage, a significant difference. Men and women, however, reacted differently. Forty-five percent of the women responded to physical therapy but 0 to general massage. In the men, the difference wasn’t statistically significant, but their response rates were higher—67 percent to physical therapy and 45 percent to massage.

Anesthetic Instillation Gets Scientific Support

Intravesical alkalized lidocaine (PSD597) offers immediate and sustained relief from the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS); results of a phase II multi-centre placebo-controlled trial

J Curtis Nickel, Kingston, ON, Canada; Michael G Wyllie, Kent, United Kingdom

Not many randomized controlled trials of therapy in IC/PBS produce positive results. This one, however, did, putting scientific weight behind instillation of alkalinized lidocaine as a valuable IC therapy. Because urine is acidic, lidocaine can stay trapped in the bladder and doesn’t get absorbed into tissue. Some way of alkalinizing it, such as using bicarbonate, converts the lidocaine to a bioavailable form. This study used a proprietary alkalinized lidocaine, called PSD597. In this multicenter study, 95 women with severe IC got the product or placebo for five consecutive days. On average, they had had IC for nearly 5 years. Neither patients nor physicians knew what they were getting. To follow their progress, patients rated how they were doing overall, rated their bladder pain and urgency, tracked their frequency, and filled out the O’Leary-Sant Symptom and Problem Index questionnaire. Eight days after treatment started, 30 percent of the patients who got the alkalinized lidocaine said they were moderately or markedly better, compared with only 9 percent of the patients who got placebo. Pain scores and symptom index scores, however, did not change significantly, although the problem index scores did. Fifteen days after the start of treatment, patients could choose another five days of treatment, and most (86 percent) did. At day 22, 63 percent of them said they were moderately or markedly better, and at day 29, 56 percent said so, suggesting that repeat instillations can improve the results. The investigators said the drug was safe, well tolerated, and had no side effects. Not only is the instillation effective immediately, but the benefits do last past treatment, they concluded.

Urodynamic Measurements Back Up Benefits of Lidocaine Instillation

Effect of intravesical lidocaine on urodynamic parameters in patients with interstitial cystitis/painful bladder syndrome (IC/PBS)

Arun K Srinivasan, Edan Y Shapiro, Casey Seideman, Robert Moldwin, New Hyde Park, NY

Lidocaine instillations are known to make IC patients feel better and improve their symptoms, and now, this study puts some concrete evidence behind it with urodynamic measurements. Eight patients who met the NIDDK research criteria for IC, which is fairly severe, got 10-minute instillations with 20 milliliters of 2 percent lidocaine. They had urodynamic measurements taken before and after. The lidocaine therapy increased bladder capacity, the maximum rate of urine flow, and how much the bladder could fill before the patient felt the need to void. The data provide more evidence for the efficacy of lidocaine instillation in patients with IC/PBS, said the researchers. They will be doing additional studies to show how the urodynamic information correlates with how patients are doing clinically.

Acupuncture Also Gets Good Scientific Support

Randomized, double blind comparison of acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic pain syndrome

Shaun W Lee, Penang, Malaysia, Men Long Liong, Kah Hay Yuen, Wing Seng Leong, Phaik Yeong Cheah, Oxford, United Kingdom, Nurzalina Abdul Karim Khan, Christopher Chee, Weng Pho Choong, Yue Wu, Wooi Long Choong, Kedah, Malaysia, Hin Wai Yap, Penang, Malaysia, John N Krieger, Seattle, WA

This study, which was published last January and covered in Café ICA, was presented here at the meeting, an impressive companion to two other studies putting some scientific weight behind physical and “alternative” therapies. Although this was a study of acupuncture treatment for men with CP/CPPS, it holds out hope for similar treatment in women and men with IC. Forty-four men got acupuncture and 45 got sham treatment in 30-minute sessions for 10 weeks. For the cleverly designed sham treatment, the technician inserted a needle half an inch away from the traditional acupuncture point and only to a short depth—less than half an inch. The points were traditional acupuncture points (CV1, CV4, Sp6, and SP9). Neither the technicians nor the patients knew who was getting the actual acupuncture treatment. The measure of response was a six-point decrease in the NIH Chronic Prostatitis Index score. At the end of 10 weeks, 73 percent of the men who had acupuncture had at least that much improvement compared with 47 percent of the men who got the sham therapy. The median decrease in the score for the acupuncture group was 11 points compared with 6 points in the sham group.

Good Science Supports E-Stim Pelvic Floor Therapy, Too

Pelvic floor electrical stimulation in the treatment of chronic pelvic pain syndrome: a randomized, sham-controlled trial

Jordan D Dimitrakov, Boston, MA, Ivan Dechev, Plovdiv, Bulgaria

This was also a study of men with CP/CPPS, but they received a therapy very similar to the electrical stimulation therapy that physical therapists use for the pelvic floor in IC patients who have pelvic floor dysfunction. For this therapy in men, electrical stimulation (using the Inova pelvic floor stimulation system from Empi) was delivered to the pelvic floor and area of the prostate through a probe inserted in the rectum. All 77 men went through “treatment” for 15 minutes twice a day every day for one month and then twice a week for 5 months, but electrical stimulation was delivered through the probe in the treatment group but not in the sham treatment group. The total scores on the NIH CPSI had dropped about 5 points at one month for the treatment group compared with about 2 points for the sham group and about 5 points at 6 months compared with about 2 points. Scores on the pain portion of the index dropped about 4 points for electrostimulation versus about 2 for sham treatment at one month and about 3 points for electrical stimulation versus about 1 point for the sham at 6 months. Also, at one month 86 percent of the electrostimulation patients said they had no pain or mild pain versus 21 percent of men who got sham treatment, and at six months, the corresponding figures were 81 percent and 25 percent—all significant differences.

Gene Therapy Could Put Body’s Own Painkiller into IC Bladders

Effects of different enkephalin treatments on bladder pain

Hitoshi Yokoyama, Chikashi Saitoh, Minoru Miyazato, Pittsburgh, PA; Osamu Nishizawa, Matsumoto, Japan; Michael B Chancellor, William F Goins, James R Goss, Joseph C Glorioso, Naoki Yoshimura, Pittsburgh, PA

Enkephalin is one of the body’s own opioid painkillers. Some rats with irritated bladders got this compound alone, and some had a gene therapy virus put into their bladders. The virus carried a gene for a precursor of enkephalin. The measure of the effect was how often the rats licked their lower abdomen and froze motionless, a sign of pain. Both the enkephalin treatment and the gene therapy reduced these behaviors. The rats who got the enkephalin had as much as an 86 percent reduction in their freezing behavior, depending on the dose. The rats that got the gene therapy had a 71 percent reduction. The researchers found that cells in the nerve roots from the level of the sixth lumbar to the first sacral vertebra, which receive signals from the bladder, showed the nerves had incorporated material from the virus. The investigators concluded that this kind of gene therapy might treat bladder pain without any side effects.

New, Selective Cannabinoid Drug May Ease Bladder Pain

Instillation of selective CB2 agonist protects against bladder irritation

Vikas Tyagi, Naoki Yoshimura, Michael B Chancellor, Pradeep Tyagi, Pittsburgh, PA

This group of researchers previously experimented with a cannabinoid drug encapsulated in liposomes (a kind of fat globule). In animals, that drug eased signs of bladder irritation. The investigators found that that drug targets two different types of cannabinoid receptors. Now, the investigators are working with a compound that targets just one of the receptors. This study aimed to show what role the cannabinoid 2 (CB2) receptor plays in bladder pain by using a CB2 agonist (a compound that mimics the natural one that triggers the receptor) and a receptor blocker in rats with irritated bladders. Rats that got the drug in their bladders were protected from the more frequent bladder spasms that irritation caused, an effect that was reversed by the receptor blocker. The researchers commented that this may help explain why marijuana-related compounds ease urinary symptoms in patients with multiple sclerosis.

Second Selective Cannabinoid Compound May Also Ease Bladder Pain

Local activation of cannabinoid CB1 receptors bladder suppresses acetic acid induced bladder irritation

Vikas Tyagi, Naoki Yoshimura, Michael Chancellor, Pradeep Tyagi, Pittsburgh, PA

In this study, the researchers used a compound that acts almost exclusively on another cannabinoid receptor, CB1. They used a CB1 agonist known as arachidonyl-2′-chloroethylamide hydrate or ACEA and a blocker in experimental animals with irritated bladders. ACEA also protected bladders from irritation, and the effect was reversed by the blocker. The researchers concluded that the CB1 agonist can buffer pain signals from the bladder.

Liposomes Stay In Bladder to Ease Symptoms

Pharmacokinetics of liposomes after intravesical administration

Jonathan Kaufman, Pittsburgh, PA

One of the preliminary studies done on any drug is a pharmacokinetic one, which looks at how and where a drug is absorbed, how much is passed out, how long it stays in the body, and more. This was a pharmacokinetic study of the liposomes, a kind of fat globule, that has been researched as an instillation treatment alone or as a carrier of a cannabinoid drug. The study found the liposomes target the bladder lining and stay in the bladder for some time, which are advantages for IC treatment.

Hot Pepper Receptor Blocking Drug Reduces Bladder Spasms

The oral TRPV1 antagonist GRC 6211 reduces bladder overactivity and noxious bladder input in cystitis

Francisco Cruz, Ana Charrua, Célia Cruz, Porto, Portugal; Shridhar Narayanan, Laxmikant Gharat, Srinivas Gullapalli, Navi Mumbai, India; António Avelino, Porto, Portugal

For some time, researchers have been focusing on a vanilloid receptor as a target for an IC drug. This receptor is the one that reacts to the hot-pepper substance capsaicin and resiniferatoxin. Researchers are now starting to look at an oral drug, now known as GRC-6211, that blocks this receptor (TRPV1) as a potential IC treatment. At a certain concentration, the drug completely stopped bladder irritation in experimental animals. At lower concentrations, it reduced the frequency of bladder contractions in response to irritation. The drug, from the Indian company Glenmark Pharmaceuticals Ltd, has been in a clinical trial for dental pain and is now being researched for nerve-related pain and osteoarthritis. Lilly will have the right to market the drug in the United States.

Thwarting Mast Cells May Dampen Bladder Inflammation

Interruption of mast cell function effectively inhibits bladder inflammation in an autoimmune cystitis model

Wu-Jiang Liu, Yi Luo, Iowa City, IA

The subjects of this study were mice with a kind of autoimmune based cystitis, which results in bladder inflammation and an increase in bladder mast cells. The mice were treated with instillations of just saline; sodium cromolyn, which is a mast-cell stabilizer; and a monoclonal antibody that interrupts activation of mast cells. Compared with saline, the mast cell treatments significantly reduced inflammation and expression of inflammatory compounds, nerve growth factor, and a precursor of substance P, a transmitter of pain signals in nerves. The treated bladders also had a much lower degree of infiltration of a type of white blood cells specific to the autoimmunity. Mast cell targeting may be useful for treating bladder inflammation with an autoimmune component (which may play a role in IC), concluded the researchers.

Botox Acts in Bladder, Not Spinal Cord, to Calm Inflammation, Spasms

Effects of botulinum toxin A on SNAP25 level and bladder function in a cyclophosphamide induced cystitis model in rats

Yao-Chi Chuang, Chou-Cheng Huang, Kaohsiung Hsien, Taiwan; Naoki Yoshimura, Pradeep Tyagi, Michael B Chancellor, Pittsburgh, PA; Po-Hui Chiang, Kaohsiung Hsien, Taiwan

Botulinum toxin A (Botox) exerts its painkilling and anti-inflammatory actions by affecting a protein called SNAP-25. This basic research showed that Botox used against bladder irritation in animals decreased inflammation and levels of SNAP25 in the bladder but not in the spinal cord. The results suggest that Botox acts locally without compromising any nerve activity in the central nervous system.

Estrogen, Serotonin Receptor Drug Eases Bladder Symptoms after “Menopause”

Estrogen deficiency causes bladder hypersensitivity via upregulation C-fiber bladder afferent nerves.

Kazuya Tanase, Nozomu Watanabe, Noriko Takahara, Keiko Nagase, Masaharu Nakai, Yoshitaka Aoki, Nobuyuki Oyama, Yoshiji Miwa, Hironobu Akino, Osamu Yokoyama, Fukui, Japan

This study of animals whose ovaries were removed to simulate postmenopause showed that replacing estrogen, but not progesterone, protected the animals from a decrease in bladder capacity prompted by potassium chloride. Giving the animals tandospirone also increased bladder capacity. Tandospirone is a 5-HT1A (serotonin) receptor agonist, used in Japan as an antianxiety medication. The researchers concluded that estrogen deficiency is related to development of bladder hypersensitivity after menopause, that long-term estrogen replacement may be beneficial for treating it, and that the hypersensitivity might depend on changes in the 5-HT receptor system in the spinal cord.

Pain Doesn’t Recur in Substituted Bladder, Sex Improves

Long term outcomes of cystectomy with bladder substitution in the treatment of advanced interstitial cystitis /bladder pain syndrome: a retrospective cohort series

Nivedita Dhar, Courtney Moore, Amit Bhatt, Adrian V. Hernandez, Craig Zippe, Sandip Vasavada, Raymond Rackley, Cleveland, OH

These clinicians assessed how 15 IC patients did long term after having a last-ditch treatment, bladder removal and substitution. At the time they filled out female sexual function and a general followup survey, they had had their surgery from 1.5 to 14 years before (average 6). Sexual function scores improved significantly. No patient had any change in bowel function, and there was no worsening of symptoms or recurrence of pain in the substituted bladders. Eleven of the 15 patients said their pain, voiding symptoms, nighttime sleep, and quality of life were markedly improved.

DIAGNOSIS/ASSESSMENT

New IC Test Shows Potential To Be Surefire

Diagnosis of interstitial cystitis using infrared microspectroscopy

Charles Anthony Buffington, Columbus, OH

Using infrared spectroscopy through a microscope, researchers found a distinctive chemical signature in the blood of humans and cats with IC. The technique distinguished those with 100 percent of the time from healthy people and cats and cats with some other disorders. This preliminary study included 29 humans and 34 cats who donated blood samples. The serum was separated and dried on microscope slides to be examined through the analytical infrared microscope. Indications are that the chemicals in the IC signature may have something to do with tryptophan metabolism. Dr. Buffington plans to test the method in larger groups and include people with other disorders. He will also try to pinpoint exactly what compounds are responsible for the characteristic IC signature.

Questionnaires May Separate IC from CP/CPPS in Men

Novel use of questionnaires to differentiate chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) from interstitial cystitis/painful bladder syndrome (IC/PBS)

Edan Y Shapiro, Casey A Seideman, Chad Huckabay, Barbara Shorter, Martin L Lesser, Julia Y Tai, Robert M Moldwin, New Hyde Park, NY

Whether IC/PBS and CP/CPPS are the same thing in men? Do they overlap, and if so, how much? Those are hotly debated questions that remain unanswered. But for now, it might be possible to differentiate between the two in men based on answers to two standard questionnaires, the NIH Chronic Prostatitis Symptom Index (NIH CPSI) and the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI). These investigators administered the questionnaires to 86 men who had been diagnosed with either IC (29 men) or CP/CPPS (56 men). The investigators then used a type of statistical analysis called “principal components analysis” to predict the patients’ answers. This analysis, which is commonly used to reduce a large number of variables down to a few, reduced the variables to just three, representing symptom severity, type of symptom (urinary or otherwise), and anatomic location. The analysis showed they could identify which condition a patient had 84 percent of the time. And, surprisingly, the most significant discriminator wasn’t the type of symptom, such as urinary frequency. Rather, it was the severity of symptoms, Barbara Shorter, RD, told the ICA.

IC/PBS Patients Do Have Urgency, But Based on Pain or Pressure

Does the symptom of “urgency” differ for women diagnosed with interstitial cystitis/painful bladder syndrome and overactive bladder?

J. Quentin Clemens, Ann Arbor, MI; Karin Liu, Laura Bogart, Sandra H Berry, Santa Monica, CA

This study represents some of the first results from the RAND Interstitial Cystitis Epidemiology (RICE) study. This analysis of the questionnaires compared urgency symptoms in women with IC/PBS and overactive bladder (OAB). The investigators found that women with both conditions had urgency, but that it was more common in women with OAB, for whom it often resulted in leaking. The feeling of urgency occurs both suddenly and gradually in both conditions. IC/PBS patients said their urgency was mainly caused by pain, pressure, or discomfort, whereas OAB patients more often said theirs was because they worried about leaking. But about half the women with OAB also said they had urgency because of pain, pressure, or discomfort.

Cystoscope with Special Imaging Shows IC Abnormalities without Hydrodistention

Flexible cystoscope with narrow band imaging system for interstitial cystitis

Tomohiro Ueda, Masayuki Nakagawa, Hideki Tanoue, Motohiro Okamura, Hiroshi Yoshida, Kyoto, Japan; Naoki Yoshimura, Pittsburgh, PA

Seeing Hunner’s lesions makes a definite diagnosis of IC, and seeing glomerulations can be an indication. Normally, the only way a urologist can see this is when your bladder is distended with fluid while you are under anesthesia. But a new flexible cystoscope with a special imaging system, called narrow band imaging, allowed doctors to see these abnormalities in the office. Although some patients can’t tolerate cystoscopy without going under anesthesia, some can with lidocaine put into the urethra or when they also go under light sedation or spinal anesthesia. The researchers looked at the bladders of 49 women and 3 men thought to have IC with this special cystoscope. The patients all got spinal anesthesia. With this cystoscope, the researchers could see ulcers and areas rich in capillary blood vessels thought likely to turn into glomerulations with hydrodistention. They also took biopsy specimens of those areas. The patients also then underwent regular cystoscopy with hydrodistention. Thirty-seven patients had ulders, which the researchers could see 100 percent of the time with the new cystoscope. Another 13 patients had capillary-rich areas that had glomerulations when the bladders were hydrodistended. Six patients had bladder cancer, which could be seen with the new cystoscope. The bladder tissue in the biopsy specimens also had high levels of a growth factor called platelet-derived endothelial growth factor (PD-ECGF), which encourages the growth of blood vessels.


EPIDEMIOLOGY

BACH Survey Ups PBS Prevalence, Highlights Needs

Beneath the illness iceberg: The magnitude of unmet urologic need in the general US population. Results from the Boston Area Community Health (BACH) Survey

John B McKinlay, Carol L Link, Watertown, MA

Urologic symptoms adversely affect people’s quality of life: Results from the Boston Area Community Health (BACH) Survey

Carol L Link, John B McKinlay, Watertown, MA

The Boston Area Community Health (BACH) Survey is still under way, but some results of early analyses were already being presented at the AUA meeting, including these two studies on prevalence of symptoms, treatment, and quality of life. The message on a number of urologic problems, including IC/painful bladder syndrome (PBS), is that physicians see only the tip of the iceberg, a small proportion of patients with the disorders. Most remain below the surface because the symptoms are not conspicuous, because inadequate health insurance discourages patients from going to doctors, or because of incorrect diagnosis. The survey asked thousands of adults in the Boston area about their urinary symptoms. Nearly half the participants had urinary symptoms, but only three percent were using medications effective for them. More men than women and more whites than blacks or Hispanics were taking medication. Data discussed in one of the presentations indicated that nearly seven percent of women have symptoms of PBS—mild, moderate, or severe (likely IC)—but that only a very small proportion were getting medications. The impact of urinary symptoms on people’s lives is great. For both men and women, the effect of urologic symptoms on their mental health was bigger than any other health problem. For women, the effect of PBS symptoms was as bad as that of diabetes and worse than cancer, stroke, arthritis, or chronic lung disease. The effect on men of prostatitis was even worse—in fact, worse than any other urologic or nonurologic condition. For women, the effect of PBS on mental health was worse than any other condition—urologic or not.

Following quickly after the meeting was publication in AUA’s Journal of Urology of BACH study results relating PBS to other conditions and medications that might be positive and negative risk factors. The analysis showed that 1.3 percent of men and 2.6 percent of women fit criteria for PBS, with increased prevalence in middle-aged adults and those of lower socioeconomic status. Men and women with PBS had depression much more often than healthy counterparts. Women also had a history of urinary tract infections, chronic yeast infections, and hysterectomy much more often than their healthy peers. They also had taken calcium channel blockers (mainly used for high blood pressure) and cardiac glycosides (used for congestive heart failure and abnormal heart rhythm) more often than their healthy counterparts. On the other hand, women who had taken thyroid medications and statins (cholesterol-lowering drugs) were less likely to have PBS symptoms. These results indicate that some of these possible risk factors could be modified to prevent or ease symptoms, similar to the way controlling risk factors such as cholesterol do in cardiovascular disease.


SOCIAL ISSUES

Frequent Nocturia Drags Down Quality of Life

Bother and impact of nocturia on health-related quality of life

Kari A Tikkinen, Tampere, Finland; Theodore M Johnson, II, Atlanta, GA; Teuvo L Tammela, Heini Huhtala, Tampere, Finland; Harri Sintonen, Helsinki, Finland; Anssi Auvinen, Tampere, Finland

Having to get up three or more times a night to urinate has a significant impact on quality of life, found these Finnish researchers who surveyed nearly 4,000 adults. In general, getting up one time a night was not bothersome for most people, two times was somewhat bothersome, but three, four, or more times was a moderate or major bother.

Not All Abuse Rates High in IC, but Depression Rate Is

A cross-sectional investigation of the prevalence of depression and abuse among women diagnosed with interstitial cystitis/painful bladder syndrome

Pegah Safaeian, Philadelphia, PA; Howard B Goldstein, Peter Finamore, Voorhees, NJ; Kristene E Whitmore, Philadelphia, PA

One hundred forty-one patients at this large IC/painful bladder syndrome (PBS) practice answered a standard depression questionnaire, a standard abuse questionnaire, and direct questions about abuse. The investigators found that 69 percent of the patients had depression, compared with the national average of only 9 percent. Thirty-six percent reported they had experienced sexual abuse during their lifetime, which is higher than the national average of 25 percent, but not that much higher, Dr. Whitmore told the ICA. The prevalence of physical abuse was 31 percent and not statistically different from the US average of 28 percent. The prevalence of emotional abuse in the patients was 57 percent, which was significantly lower than the US average. There was a discrepancy between the rates of abuse the investigators found based on the questionnaire and the patients’ answers to simple questions about abuse. Dr. Whitmore emphasized that doctors should refer women who have been abused for counseling if they need it, but that it doesn’t mean IC has a psychological cause and doesn’t mean that their pain shouldn’t be well controlled with medication.

VA Study Links Sexual Trauma to Urinary Tract Symptoms

Sexual trauma and psychiatric comorbidities in women with lower urinary tract symptoms (LUTS)

Adam P Klausner, Benjamin W Herrick, Vernon Orton, Ashley B King, Diane Ibanez, Daniel L Willis, Luke Wolfe, B Mayer Grob, Richmond, VA

Women who went to a specialized urology clinic for lower urinary tract symptoms (LUTS), such as those of overactive bladder, IC, or incontinence, were screened for sexual trauma, and their answers were compared with those of women going to a general medical clinic. The 115 women with LUTS and the 1,300 women were all asked, “Have you ever been forced to have sex against your will?” because the VA has made it a policy to screen all women, said the presenter. The control women were also asked if they had any LUTS symptoms. Results of surveys showed that 22 percent of the control women had experienced sexual trauma, 28 percent had a coexisting psychiatric condition, and 24 percent had LUTS. Of the women who went to the urology clinic, the rate of sexual trauma was much higher—48 percent—and the rate of coexisting psychiatric conditions was also higher—65 percent. Patients who had experienced sexual trauma and who had coexisting psychiatric conditions had poorer quality of life. Neither trauma nor psychiatric condition was related to the type and severity of incontinence. In this session, chairman Raymond Rackley, MD, from the Cleveland Clinic and Robert Evans, MD, from Alliance Urology Specialists in Greensboro, North Carolina, were concerned about jumping to the conclusion that sexual trauma causes urinary tract problems, worrying that it might divert physicians from effective management. Dr. Rackley also expressed the concern that patients might not respond accurately to the question about sexual trauma because it is being asked so often.

Easing Bladder Pain Can Improve All Aspects of Sex

Female sexual function improves in treated interstitial cystitis patients

Blayne K Welk, Joel M Teichman, Vancouver, BC, Canada

IC/PBS impairs every aspect of a woman’s sexual function, which has a huge impact on quality of life. A recent study showed that pain with intercourse gets better with instillations of lidocaine, bicarbonate, and heparin. Now, these researchers have shown that when pain with intercourse improves, so do other aspects of sexual function, such as desire, arousal, orgasm, and satisfaction. Women who didn’t get relief of pain with intercourse also did not have their urinary symptoms improve as much. The patients who did best with this treatment tended to have lower scores on the Pelvic Pain, Urgency Frequency (PUF) Scale and bladder neck tenderness alone (without multiple tender spots in the pelvic floor) at the outset.

Foods, Beverages Affect Men with Pelvic Pain, Too

The effects of foods, beverages and supplements on the symptoms of chronic prostatitis/chronic pelvic pain syndrome

Barbara Shorter, Brookville, NY, Lesser Marty, Julia Tai, Manhasset, NY, Dolorita DeJesus, New Hyde Park, NY, Sheetal Kapadia, Brookville, NY, Casey Seideman, Robert M Moldwin, New Hyde Park, NY

These investigators previously validated what IC patients have known, that certain foods and beverages exacerbate symptoms. Now, they have extended their study to men with pelvic pain, although in this analysis, they said during their presentation, they did not distinguish between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and IC. The men answered the same questionnaires as in the previous studies, which asked whether more than 170 different food items worsened symptoms, had no effect, improved symptoms, or wasn’t part of the patient’s diet. The men also answered the NIH CPSI questionnaire. Of the 15 patients who had the worst symptoms, 11 (73%) said certain foods and beverages did exacerbate symptoms. Of the 15 patients with the least severe symptoms, only 2 (13 percent) said they were food sensitive. Foods indicating the greatest effect on worsening symptoms were the same as those found in the IC study. The top eight, in order, were coffee, tea, alcohol, citrus fruits, spicy foods, hot pepper, tomato products, and carbonated beverages.


BASIC RESEARCH

Pain Fiber Sensitivity Correlates with Length of IC Symptoms

Evaluation of neuroselective current perception threshold in patients with overactive bladder or interstitial cystitis indicated coexistence of hypersensitivity in bladder afferent A-delta and C fibers

Osamu Ukimura, Naoki Hirahara, Yasuhiro Yamada, Hisashi Honjo, Atsuko Fujihara, Daisuke Toiyama, So Ushijima, Koji Okihara, Yoichi Mizutani, Akihiro Kawauchi, Tsuneharu Miki, Kyoto, Japan

Using a special instrument in the bladder that measures the response of nerves to electrical stimulation, these investigators measured how two different types of pain-sensing nerve fibers function in patients overactive bladder (OAB) and with IC. The instrument measures how strong the impulse needs to be for the patient to sense something, called the “current perception threshold” or CPT. In IC patients with treatment-resistant disease, the degree of hypersensitivity of the C fibers correlated with their having had symptoms longer and having had multiple treatments, such as hydrodistention (with glomerulations found). Patients with treatment-resistant IC who had C fibers that were not very sensitive had had their symptoms for a shorter time and had had fewer therapeutic procedures done.

Colon-Bladder Connection May Explain Mast Cells and Leaky Bladder Lining

Neurogenic cystitis induced by colonic irritation results in increased urothelial permeability that parallels bladder mastocytosis and hyperactivity

Elena E Ustinova, Dmitriy W Gutkin, Pittsburgh, PA; Matthew O Fraser, Durham, NC; Michael A Pezzone, Pittsburgh, PA

In previous research, these investigators found that irritation of the colon sensitizes the bladder, leading to IC-like urination patterns and sensitivity to physical and chemical irritants. Afterward, large numbers of mast cells came into both the colon and bladder. Now, this team has looked at the relationship between that phenomenon and the permeability or “leakiness” of the bladder lining, which would allow nerve irritation. They found that colonic irritation in anesthetized animals did indeed increase the permeability of the bladder along with the increase in the numbers of mast cells and an increase in frequency. Those events look like the self-progressing state of IC in many patients.

Mast Cells Promote Pain

Mast cell-derived histamine mediates cystitis pain

Charles N Rudick, Paul J Bryce, Laura A Guichelaar, David J Klumpp, Chicago, IL

Mast cells have been implicated in the IC process, but what role they play isn’t clear, so these researchers looked at pain behavior in mice genetically engineered to lack mast cells and normal mice. The mice had an infection that gave them a nerve-related cystitis that looks very much like IC. Some of the mice that lacked mast cells were later treated with bone marrow transplants so they could make mast cells. Mice lacking mast cells demonstrated less pain behavior, despite their IC like condition. Antihistamines reduced pain in the mice that did have mast cells. The researchers concluded that mast cells cause cystitis pain and that histamine receptors may be good targets for pain drugs.

Alpha Estrogen Receptor May Play Role in IC Symptoms, Pain

Altered urinary bladder function and impaired nociception in mice lacking estrogen receptor-α

Zunyi Wang, Peiqing Wang, Dale E Bjorling, Madison, WI

Does estrogen play a role in bladder pain? This research aimed to answer that question by looking at the effects of bladder irritation in mice genetically engineered to lack one or the other of the two kinds of estrogen receptors. Mice lacking the alpha estrogen receptor normally urinated more frequently than mice without the beta receptor or wild mice. When bladders were irritated, the wild mice and the mice without the beta receptor had increased bladder contractions and sensitivity to touch on their hind paws, but the mice lacking the alpha receptor did not. Lack of either receptor did not affect bladder inflammation. That lack of the alpha receptor prevents increased pain perception in peripheral parts of the body when bladders are irritated is a new finding and may help explain differences in cystitis patients’ perception of pain, the investigators concluded.

Bladder Autoimmunity Produces IC-like Condition

Bladder function of experimental autoimmune cystitis in mouse

Guiming Liu, Yi-Hao Lin, Michael Kavran, Cengiz Z Altuntas, Vincent K Tuohy, Firouz Daneshgari, Cleveland, Ohio

IC in some patients is thought to have an autoimmune connection because autoimmune disease is more common in IC patients than in the general population. To take a closer look at what this connection might be, these researchers found a way to induce autoimmunity to bladder tissue in mice. With an autoimmune reaction, the mice had bladders that looked like IC bladders and had IC-like symptoms. The layer just under the bladder lining was thickened and had infiltrations of white blood cells, and the bladder muscle had increased numbers of mast cells. The mice also had increased urinary frequency, decreased amounts of urine with each void, and more frequent bladder muscle contractions. The similarity suggests that immune mechanisms may be at work in IC, said the researchers.

Posted May 17, 2010