Overview of AUA Interstitial Cystitis/Painful Bladder Syndrome Session

For the first time in memory, the session devoted to interstitial cystitis at the annual meeting of the AUA was a podium session rather than a poster session. A mix of basic science and clinical presentations resulted in a compelling presentation.

Yokoyama and colleagues from Matsumoto Japan and Pittsburgh examined the antinociceptive effects of systemically administered enkephalin, a d-opiod receptor agonist as well as gene therapy using herpes simplex virus vectors expressing preproenkephalin, the precursor of enkephalin, using a rat model of bladder pain. Their data indicated that both types of enkephalin treatments via systemic administration or herpes simplex virus-mediated gene transfer are effective to suppress bladder pain induced by bladder irritation. Enkephalin gene therapy could be a potential treatment of bladder pain.

Ustinova and co-workers from Pittsburgh and Durham hypothesized that chronic mast cell infiltration of pelvic organs following an acute pelvic organ insult may play a role in chronic pelvic organ sensitization and cross-sensitization. They hypothesized that pelvic organ mastocytosis maintains increased epithelial permeability leading to direct afferent activation by physiologic stimuli. In an animal model they presented data indicating that neurogenic sensitization of bladder afferents by colonic irritation of divergent afferents that innervate both colon and bladder and dorsal root reflexes results in simultaneous mast cell attraction and urothelial barrier breakdown (based on potassium and fluorescein absorption). Further sensitization of submucosal afferents then causes a vicious cycle, attracting more mast cells and resulting in increased breakdown of barrier function.

Liu and Luo from Iowa City showed that interrupting mast cell function in a mouse model of bladder inflammation effectively alleviates autoantigen-mediated bladder inflammation. They went on to hypothesize that mast cell targeting may be a useful approach for treating bladder inflammation with an autoimmune component such as IC. Rudick and co-workers from Chicago used a pseudorabies virus induced neurogenic cystitis model to examine the underlying molecular basis of pelvic pain. Their data in a mouse model suggested that mast cells cause cystitis pain and bladder inflammation through the separable actions of histamine and tumor necrosis factor. They believe that histamine receptors may be valid therapeutic targets for pelvic pain therapy.

Three presentations examined intravesical lidocaine treatment of the painful bladder. Srinivasan and colleagues from New York observed the effect of 20cc of 2% intravesical lidocaine 10 minute exposure on urodynamic parameters in 8 patients. Bladder capacity, peak flow rate, and first urge to void showed improvement. Nickel and colleagues from Kingston, Ontario and Kent, UK reported the results of a phase 2 trial of an intravesical alkalinized lidocaine solution in IC/PBS. Five consecutive daily instillations were compared to placebo instillations at 19 North American centers with 102 patients randomized. Interval follow-up to day 29 was performed. At 8 days after the 5 day treatment course, 30% of active patients rated their improvement as moderately or markedly improved vs 9.6% on placebo. Welk and Teichman from Vancouver reported on female sexual function in IC patients. Their data in 32 consecutive IC patients with dyspareunia treated with intravesical alkalinized lidocaine and heparin compared multiple sexual domains before and 4 weeks after a course of therapy. 50% of subjects had resolution of dyspareunia and corresponding improvement over several sexual domains. Those with tenderness of the bladder neck alone prior to therapy had the best outcomes.

Jonathan Kaufman from Pittsburgh studied the pharmacokinetics of liposomes after intravesical administration. He concluded that intravesical delivery of empty liposomes provides a significant bladder urothelium targeting advantage with long bladder residence time of 24 hours. These pharmacokinetic studies support the use of empty liposomes as a potential local therapy for painful bladder/interstitial cystitis.

Chuang and colleagues from Taiwan and Pittsburgh presented a paper on the mechanism of analgesia and anti-inflammatory properties of botulinum toxin A in a rat model. They concluded that botulinum toxin A intravesically decreased SNAP-25 level in the bladder, but not in the spinal cord. It inhibited cyclophosphamide induced bladder inflammation and hyperactive bladder. This suggests a local neuromodulation of botulinum toxin A on the bladder without compromise of central neurotransmission.

Wang and co-workers from Wisconsin studied altered urinary bladder function and impaired nociception in mice lacking estrogen receptor-a. The absence of estrogen receptor-a prevented increased peripheral pain perception associated with cystitis, and may help to explain patient differences in perception of pain associated with cystitis.

Diagnosis received attention at this meeting. Ueda and colleagues from Kyoto and Pittsburgh showed that a flexible cystoscope with a narrow band imaging system can detect mucosal angiogenic lesions. In a study of 52 patients, 37 cases were found to have ulcers by conventional cystoscopy under anesthesia. All cases were identified without hydrodistention by the narrow band imaging flexible cystoscopy, and were found to be associated with platelet derived endothelial growth factor on biopsy specimens. The group concluded that this new endoscopic system will make it unnecessary to do cystoscopy with anesthesia to discover the typical Hunner’s lesion. Buffington in Columbus, Ohio assessed the feasibility of using infrared microspectrosopic analysis (IRMS) of dry serum films for diagnosis of IC in cats and humans. Specific infrared bands discriminated IC from healthy subjects in both species. His data suggested that intermediate compounds in the metabolism of tryptophan might be associated with the pathophysiology of IC.

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