ORL-1 AND MU-OPIOID RECEPTOR ANTISERA LABEL DIFFERENT FIBERS IN AREASINVOLVED IN PAIN PROCESSING

Mu opioid receptors (MOR) mediate the analgesic effects of opioid drug s such as morphine. The opioid receptor-like (ORL-1) receptor is struc turally related to opioid receptors and the ORL-1 receptor agonist, or phanin FQ/nociceptin, induces analgesia at the spinal level, but appea rs to recruit different circuitry than that used by mu opioids. When a dministered intracerebroventricularly, orphanin FQ/nociceptin produces hyperalgesia and/or reverses opioid analgesia. The functionally disti nct actions elicited by MOR and ORL-1 receptors, which activate simila r intracellular signaling systems and show similar regional distributi ons, could be explained by their differential cellular localization. B y using double label immunohistochemistry and confocal microscopy, the present study investigates the distribution of MOR and ORL-1 receptor s in regions of the rat nervous system that are involved with nocicept ive processing. In general co-localization of MOR and ORL-1 receptor i mmunoreactivity was not observed in either perikarya or neuropil in th e dorsal root ganglia, nor in the Lissauer's tract and superficial lam inae of the spinal cord. Likewise, there was no evidence for co-locali zation of these receptors within the periaqueductal gray, the nucleus raphe magnus, the gigantocellular reticular nucleus, and the nucleus o f the solitary tract. These observations indicate that MOR and ORL-1 r eceptors are expressed predominantly on different fiber systems in the se regions. This differential distribution is consistent with the dist inct pharmacology of ORL-1 and MOR receptor agonists and suggests that the antisera to MOR and ORL-1 receptors may provide useful markers fo r further investigations of analgesic and counteranalgesic pathways mo dulating pain perception. (C) 1988 Wiley-Liss, Inc.