Nociceptin protects capsaicin-sensitive afferent fibers in the rat urinarybladder from desensitization

Chemical stimulation of primary afferent nerves in the rat urinary bladder in vivo with topical capsaicin (I pg in 50 mu l saline) determines a dual m otor response, consisting of a contractile effect mediated by tachykinins r eleased from sensory nerves in the bladder wall and a transient activation of a bladder-to-bladder micturition reflex organized at the supraspinal lev el (chemoceptive micturition reflex). Both responses undergo complete desen sitization upon repeated applications of capsaicin. The i.v. administration of the novel neuropeptide nociceptin (100 nmol/kg) produced a long-lasting protection from capsaicin desensitization of afferent nerves which mediate the chemoceptive micturition reflex. In fact a chemoceptive micturition re flex could be repeatedly evoked by topical capsaicin in nociceptin-pretreat ed rats. In sharp contrast, nociceptin did not influence the development of desensitization of the local response to capsaicin, corresponding to the ' efferent' function of capsaicin-sensitive afferent neurons. These results s uggest that the afferent and 'efferent' function of capsaicin-sensitive pri mary afferent neurons (CSPANs) in the rat bladder are differentiated by noc iceptin. Alternative mechanisms underlying this phenomenon are discussed.