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
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