Nociceptin and the micturition reflex

The i.v. administration of nociceptin (10-100 nmol/kg) inhibits the micturi tion reflex in a naloxone-resistant manner. The effects induced by i.v. noc iceptin were not observed in capsaicin-pretreated animals indicating that i .v, nociceptin inhibits the micturition reflex by inhibiting afferent disch arge from capsaicin-sensitive nerves. Supporting this interpretation, nocic eptin also inhibited the reflex but not the local bladder contraction induc ed by topical capsaicin and protects this reflex (but not the local contrac tion) by desensitization. Intrathecal nociceptin (10 nmol/rat) produces uro dynamic modifications similar to those induced by the i.v. administration. Intracerebroventricular (i.c.v.) administration of nociceptin (0.3-1 nmol/r at) also inhibited the micturition reflex in a naloxone-resistant manner su ggesting a direct effect on supraspinal sites controlling the micturition. Beyond the inhibitory effects exerted by nociceptin on the micturition refl ex, a peripheral excitatory effect mediated by capsaicin-sensitive fibers w as also detected. The application of nociceptin (5-50 nmol/rat) onto the bl adder serosa when the intravesical volume was subthreshold for the triggeri ng of the micturition reflex, activated the reflex in a dose-dependent mann er; the same treatment produced a biphasic effect on the ongoing reflex. In addition to the triggering of micturition reflex, topical nociceptin evoke s a local tonic-type contraction that was abolished by the coadministration of tachykinin NK, and NK, receptor antagonists. Altogether these results i ndicate that ORL1 receptors are present at several sites for the integratio n of the micturition reflex, and that their activation may produce both exc itatory or inhibitory effects, depending on the route of administration and the experimental conditions. (C) 2000 Elsevier Science Inc. All rights res erved.