Bladder afferents and their role in the overactive bladder.

The role of afferent innervation of the bladder in the pathophysiology of urinary incontinence has become the focus of intense interest. In normal health, the afferent pathway is mediated largely by Adelta-fibers, which ultimately send information about the state of bladder fullness to the pontine micturition center via the periaqueductal gray matter. However, after spinal disruption, a different type of afferent pathway emerges, mediated by capsaicin-sensitive C-fibers that drive a spinal segmental reflex pathway, causing neurogenic detrusor overactivity. The common sources of afferent information for either pathway are likely to be afferents from the urothelium, lamina propria, and afferents that originate in the bladder wall. Ultrastructural investigations of the constituent neural elements of these structures contribute to our knowledge of their role in both health and disease and help provide a rational approach to treatment strategies. Evidence of the involvement of capsaicin-sensitive C-fibers in the spinal reflex pathway has been supported by the successful treatment of patients with neurogenic incontinence with intravesical capsaicin or its ultrapotent nonpungent analog, resiniferatoxin. On the other hand, capsaicin has not been shown to be clearly effective in treatment of overactive bladder caused by detrusor overactivity or suprapontine pathology without the emergent C-fiber-mediated reflex. It is hoped that continued investigation of neurotoxins that have the potential to act on afferent innervation will lead to other treatment strategies for bladder disorders and other disorders involving afferent dysfunction.