Interstitial cystitis: diagnosis and treatment options.

Interstitial cystitis (IC) is a disease complex characterized by urinary frequency, urgency, and bladder pain without an identifiable cause. Essentially, IC is a diagnosis of exclusion. The lack of knowledge of pathophysiology remains the biggest hurdle in diagnosis and treatment of this puzzling and troublesome disorder. Nevertheless, several recent advances, coupled with increased public awareness of this disease, make it easier for physicians and patients to effectively deal with IC.

Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia.

OBJECTIVES: Recent data suggest that the bladder urothelium may have a sensory function by way of release of adenosine triphosphate (ATP) during stretch, which then acts as a sensory neurotransmitter. Because benign prostatic hyperplasia (BPH) can give rise to irritative (hypersensory) voiding patterns, we questioned whether the bladder urothelium from patients with BPH released more ATP during in vitro stretch and whether doxazosin, an alpha(1)-adrenoceptor blocker, affects this purinergic mechanism. METHODS: Bladder urothelial biopsies from patients with BPH (n = 4) and controls (n = 4) were cultured using established techniques. In vitro stretch was performed with a Flexcell 2000 device that uses vacuum to deform the cell growth surface to impart a stretch force. Doxazosin (5 microM and 20 microM) was added to cells, and supernatants were collected at various points for ATP assay. ATP was assayed using the luciferin-luciferase reaction. ATP data were normalized to the time 0 value and expressed as a percentage of the baseline value. RESULTS: After 96 hours of stretch, the BPH urothelial cells released significantly more ATP than did the control urothelial cells (62.6% +/- 11.2% versus 24.2% +/- 5.4%, P = 0.005) and nonstretched BPH urothelial cells (62.6% +/- 11.2% versus 15.1% +/- 5.1%, P = 0.004). The augmented release of ATP by stretched BPH bladder urothelial cells was completely blocked by treatment with 20 microM doxazosin. CONCLUSIONS: Irritative voiding secondary to BPH may arise from increased ATP release by bladder urothelium during stretch. Doxazosin inhibits ATP release by way of an unknown mechanism that may or may not involve the alpha1-adrenoreceptor. Treatment for hypersensory voiding symptoms secondary to BPH might also target the urothelial purinergic pathway.

Sacral neuromodulation for the treatment of bladder dysfunction.

S3 nerve root neuromodulation is becoming an accepted therapy for individuals afflicted with lower urinary tract symptoms, such as idiopathic urinary urge incontinence, frequency, urgency, and urinary retention, who fail current standard therapies. This patient population is difficult to treat, and this therapy offers an option that can restore quality of life to these individuals. While the precise pathophysiologic mechanisms underlying these voiding symptoms is unknown based on the physiology of bladder function, it is logical to conclude that they relate to some aberration of the neuromuscular apparatus of the bladder and/or its outlet (the urethra). These pathophysiologic defects are not overtly manifested outside the lower urinary tract because these patients routinely do not have any apparent neurologic deficits. The fact that S3 neuromodulation can clinically improve these lower urinary tract symptoms would support the notion that the neural regulation of the bladder is somehow altered in these patients. This paper presents a review of the current knowledge regarding sacral neuromodulation in treatment of non-neurogenic voiding dysfunction.