(Author: Phil Hanno MD -
www.urotoday.com)
CHICAGO, IL, USA - The poster session on Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) highlighted many interesting presentations and engendered several thoughtful discussions. Both basic science presentations and clinical presentations were included in the session. The range of interest in the disorder continues to expand as specialties other than urology and gynecology are focusing on BPS/IC as one of a group of pain syndromes possibly related to similar syndromes in their other medical specialties.
Curtis Nickel reported data from the Interstitial Cystitis Deep Phenotyping Research Group that confirms the relationship of BPS/IC to other chronic pain syndromes. Irritable bowel syndrome was self-reported in 38.7% of patients vs. 5.6% of controls, fibromyalgia was self-reported in 17.6% of patients vs., 1.7% of controls, and chronic fatigue syndrome in 9.4% vs. 1.1% respectively. No other pain condition was found in 52.4% of the BPS/IC patients studied. Symptom duration was associated with phenotypic expression. Whether that last finding holds up over time will be interesting as will the potential impact of treatment on phenotypic expression.
Herati and co-workers from New York compared
food sensitivities between interstitial cystitis patients and chronic prostatitis patients and found that the former group is more likely to have food and beverage sensitivity.
Sandra Berry reported prevalence data from the 5 year Rand Interstitial Cystitis Epidemiology study that was just completed. Using an academically and statistically rigorous technique, they found that 2.5-2.7% of the population of United States women meet a high specificity symptom definition suggesting BPS/IC. Taking into account all factors including false positive and false negative calculations, the prevalence estimate among women in the US using a higher specificity epidemiologic definition for the disease was 2.7%. Using an epidemiologic definition with higher sensitivity, prevalence was 6.5%. This translates to a prevalence of women over 18 years of age in the United States who have symptoms compatible with BPS/IC of 3.4-7.9 million, significantly higher than most previous prevalence estimates. Both the Boston Area Community Health Project and the Rand group are looking at rates of spontaneous resolution of symptoms among these populations in the year after initial survey, and those results should be available in the next 12-16 months. They should prove very interesting as well.
Two studies on the use of
botulinum toxin A (BoNT-A) were presented. Pinto and colleagues from Portugal injected 17 patients with an intra-trigonal technique, using ten 10 unit injections. Three month results were excellent in terms of pain, frequency, and O’Leary Sant scores. At 9 months 7 patients requested another botulinum toxin A injection. Kuo’s group from Hualien, Taiwan and Chancellor from Royal Oak, Michigan compared hydrodistention under anesthesia alone (n=23) to hydrodistention 2 weeks after suburothelial injection with 200u (n=15) or 100u of BoNT-A (n=29). At 1 year the success in the BoNT-A group was 54.6% compared to 26.1% in the control group. BoNT-A success fell to 30% at 2 years. Of note, all patients were permitted to continue baseline medication.
Several other treatments were also discussed.
Urine alkalinization, generally a part of the conservative management of BPS/IC, was shown to improve pain scores and diminish nocturia in a prospective study of 50 patients with BPS/IC treated with citrates by Ueda and coworkers in Kyoto, Japan.
Reeves and colleagues in Sheffield, UK retrospectively studied acupuncture results in 15 symptomatic patients. Using measure yourself medical outcome profile visual analogue scores, quality of life improved in 86% of patients after 1-6 sessions. One hundred percent of patients had symptom improvement. No sham control was included.
Tsuchida and coauthors from Chuo, Japan explored the effect of the Chinese herbal medicine containing aconitine in 10 IC patients who had failed standard therapies. Aconitine is a highly poisonous alkaloid derived from various aconite species. It is a neurotoxin that opens TTX-sensitive Na+ channels in the heart and other tissues, and is used for creating models of cardiac arrhythmia. They found that Keisika-jutsu-buto and Mao-bushi-saisinto were effective in relieving pain and increasing bladder capacity. Whether it might be possible to pharmacologically alter the active ingredient to make it safe to use as a prescription drug remains to be seen.
Harris, Cheng, and Liebert from Ann Arbor, Michigan performed in-vivo studies in cultured human urothelial cells using all-trans-retinoic acid (ATRA), a differentiation-inducing retinoid, to see if it could increase heparin binding epidermal growth factor like growth factor (HB-EGF), which is inhibited by antiproliferative factor, a putative causative agent in BPS/IC. Their findings did show their hypothesis to be valid. To the extent that BPS/IC patients have low HB-EGF levels in urine, it is possible that ATRA could have some therapeutic value.
Another potential therapy could be intravesical chondroitin sulfate, a glyocaminoglycan. Sofinowski and colleagues from Oklahoma City showed that when intravesically applied in rodent bladders damaged by exposure to hydrochloric acid, it binds specifically to damaged bladder and restores urothelial impermeability to levels similar to controls.
Jacobs and co-workers form Pittsburgh measured urinary nerve growth factor in a wide range of patients with a spectrum of urologic diagnoses. They reported that urinary nerve growth factor levels were highest in patients with neurogenic overactive bladder and BPS/IC and in women with conditions typically associated with lower urinary tract symptoms.
Human bladder tissue studies in BPS/IC patients and controls revealed that tachykinin receptors NK1 and NK2 are down-regulated in the dome of IC patients. Sanchez-Freire and colleagues from Bern, Switzerland postulated that, in contrast to acute inflammatory states, continuous exposure to mediators of neurogenic inflammation in BPS/IC induces re-modeling of the receptor signaling complex.
Goo from Seattle reported work from his group that suggests that urinary proteomics may be able to characterize interstitial cystitis through qualitative and quantitative differences in the urinary proteome which result from IC-induced disruption of urothelial integrity. Tyagi and colleagues in Pittsburgh and Michigan found elevated levels of specific chemokines in the urine and correlated them with increased severity of IC symptoms. A Japanese study (Ogawa et.al.) investigated the genes responsible for the ulcerative form of BPS/IC and found over-expression of genes involved in cell to cell communication and signaling, inflammatory disease, and cellular development.
A rat study from Yoshimura’s Pittsburgh lab presented by Yunoki concluded that Kv4.1 and/or 4.3 subunits are involved in the formation of A-type potassium channels in somatic C-fiber dorsal root ganglion neurons, but not in bladder afferent neurons, making the Kv4 channel a more suitable candidate for somatic rather than bladder pain. Yokoyama, also from the University of Pittsburgh examined the results of gene therapy in a rat model using NP2, which is a newly engineered replication-deficient herpes simplex virus vector expressing human preproenkephalin. A reduction in bladder hyperactivity via opioid receptor in the spinal cord blocked nociceptive responses after resiniferatoxin administration into the bladder.
Susan Keay and colleagues from Maryland updated their work on antiproliferative factor (APF). They have screened inactive synthetic APF derivatives for their ability to inhibit APF in normal bladder cells, and are looking at the ability of inhibitory derivatives to normalize tight junction protein gene expression, paracellular permeability, and/or proliferation of IC cells.
As the knowledge of the prevalence and importance of bladder pain syndrome/interstitial cystitis increases, further research into both clinical and basic science aspects of this syndrome can be expected as the field continues to advance.
Presented at the Annual Meeting of the American Urological Association (AUA) - April 25 - 30, 2009 - McCormick Place Convention Center - Chicago, Illinois, USA.
