Endogenous nociceptin signaling and stress-induced analgesia

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawa l assay was performed in mice stressed by forced swimming in water at 15 de greesC (high severity swims) or 32 degreesC (low severity swims). High seve rity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (I nmol). The selective OP4 receptor antagonist, [Nphe(1)]]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that wa s partially antagonized by naloxone, completely blocked by NC and potentiat ed by [Nphe(1)]NC(- 13)NH2. These findings confirm the anti-analgesic role of supraspinal NC and suggest that endogenous NC signaling counteracts the opioid component of SIA. NeuroReport 12:3009-3013 (C) 2001 Lippincott Willi ams & Wilkins.