Capsaicin-sensitive nerves sense bladder fullness and form the afferent limb of the micturition reflex . In conditions of bladder hypersensitivity, TRPV1 is up-regulated on these nerves (presumably via NGF [133, 134]) and 'deafferentation' of the bladder by intravesical capsaicin or RTX was proven beneficial [135-137]. Parenthetically, intravesical RTX is also an effective analgesic agent during experimental cystitis in the rat . By contrast, intravesical RTX is without therapeutic benefit in patients with interstitial cystitis . This is an important reminder that efficacy in animal models does not necessarily translate into benefit in patient!
The expression of TRPV1 in the bladder is, however, not restricted to afferent nerves: urothelium, detrusor muscle and fibroblasts also express TRPV1 in the human bladder . The implication of these findings for intravesical vanilloid therapy is unclear , but the increase in TRPV1 immunoreactivity in the urothelium in patients with neurogenic detrusor overactivity (that occurs in concert with increased TRPV1 in bladder afferents) is a very intriguing finding . In the male urogenital system, TRPV1 is also present in testicles, prostate and scrotal skin , and it was postulated that TRPV1 ligands may be beneficial in the treatment of benign prostatic hyperplasia .
It is very likely that similar mechanisms also play a central role in the development of faecal incontinence. In fact, enhanced TRPV1 expression was demonstrated in patients with faecal incontinence .
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