TY - JOUR T1 - Antianalgesic Action of Nociceptin Originating in the Brain Is Mediated by Spinal Prostaglandin E<sub>2</sub> in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 7 LP - 14 VL - 296 IS - 1 AU - Jodie J. Rady AU - William B. Campbell AU - James M. Fujimoto Y1 - 2001/01/01 UR - http://jpet.aspetjournals.org/content/296/1/7.abstract N2 - 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 PGD2. 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. U.S. Government ER -