ORPHANIN FQ ACTS AS A SUPRASPINAL, BUT NOT A SPINAL, ANTI-OPIOID PEPTIDE

ORPHANIN FQ (OFQ), the endogenous ligand for the orphan opioid recepto r, LC132, was recently isolated and characterized. The anti-opioid rol e of OFQ in supraspinal pain modulation was demonstrated by our previo us observations that intracerebroventricular (i.c.v.) OFQ administrati on dose-dependently reverses systemic morphine antinociception and opi oid-mediated stress-induced antinociception. The present study was des igned to evaluate whether OFQ also modulates the antinociceptive actio ns of morphine in the spinal cord. Immediately after assessment of bas eline nociceptive sensitivity on the 49 degrees C tail-withdrawal assa y, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktail s of morphine (0, 1, 10 or 50 mu g [0-135 nmol]) and OFQ (0 or 10 nmol ), and re-tested 15, 30 and 60 min later. OFQ alone did not affect noc iceptive sensitivity when administered by either route. Following i.c. v. administration, the antinociception produced by 10 mu g morphine wa s completely reversed by 10 nmol OFQ; antinociception induced by 50 mu g morphine was significantly antagonized. In contrast, OFQ was comple tely ineffective against antinociception induced by i.t. morphine. the se findings indicate that the anti-opioid actions of OFQ are restricte d to supraspinal central nervous system sites.