Abstract

An antianalgesic action of intracerebroventricularly administered nociceptin was elicited against intrathecal morphine-induced antinociception in the tail-flick test in mice and investigated as a descending neuronal system for the spinal mediator involved. The nociceptin-induced antianalgesia originating in the brain was inhibited by intrathecally administered indomethacin and suggested the mediation of spinal prostaglandin. The antianalgesic action of intracerebroventricular nociceptin was closely matched by intrathecal prostaglandin (PG) E₂. Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD_2. Desensitization of the antianalgesic action of PGE₂ by intrathecal PGE₂ pretreatment also produced cross-desensitization to the antianalgesic action of intracerebroventricular nociceptin. Neither intracerebroventricular nociceptin nor intrathecal PGE₂ produced antianalgesia against the δ-receptor agonists given intrathecally. Thus, the antianalgesic action of nociceptin originating in the brain is coupled to a descending neuronal pathway mediated by spinal PGE₂.