Nociceptin and dynorphin A(1-17) produce antianalgesia through independent systems in mice

The administration of dynorphin A(1-17), Dyn, intrathecally (i.t.) or of nociceptin, intracerebroventricularly (i.c.v.) produces antianalgesic actions against i.t. morphine in the tail flick test in mice. The antianalgesic action of nociceptin is mediated by spinal PGE2 and attenuated by i.t. PGD2 or indomethacin. The Dyn response is mediated by release of IL1beta in the spinal cord to activate an ascending pathway to the brain and in turn releases IL1beta in the brain which activates a descending pathway to the spinal cord. The present work investigated the possibility that the action of IL1beta in the Dyn system might release prostaglandins so that the Dyn and nociceptin antianalgesic systems would overlap at these points. The results indicated that in the Dyn system neither the IL1beta in the spinal cord or brain implicated prostaglandin release because i.t. and i.c.v. PGD2 and indomethacin did not affect Dyn-induced antianalgesia. In addition, nociceptin-induced antianalgesia did not involve components in the Dyn system. Thus, the Dyn and nociceptin antianalgesic systems did not overlap and each were independent systems.