Antianalgesic action of nociceptin originating in the brain is mediated byspinal prostaglandin E-2 in mice

An antianalgesic action of intracerebroventricularly administered nocicepti n was elicited against intrathecal morphine-induced antinociception in the tail-flick test in mice and investigated as a descending neuronal system fo r the spinal mediator involved. The nociceptin-induced antianalgesia origin ating in the brain was inhibited by intrathecally administered indomethacin and suggested the mediation of spinal prostaglandin. The antianalgesic act ion of intracerebroventricular nociceptin was closely matched by intratheca l prostaglandin (PG) E-2. Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD(2). Desen sitization of the antianalgesic action of PGE(2) by intrathecal PGE(2) pret reatment also produced cross-desensitization to the antianalgesic action of intracerebroventricular nociceptin. Neither intracerebroventricular nocice ptin nor intrathecal PGE(2) produced antianalgesia against the delta -recep tor agonists given intrathecally. Thus, the antianalgesic action of nocicep tin originating in the brain is coupled to a descending neuronal pathway me diated by spinal PGE(2).