Effects of nociceptin (13–17) in pain modulation at supraspinal level in mice

This work was designed to observe the effects of nociceptin(13–17), one of the main metabolites of nociceptin (also termed orphanin FQ), in pain modulation at supraspinal level in mice. Intracerebroventricular (i.c.v.) administration of nociceptin/orphanin FQ(13–17) (N/OFQ(13–17)) (5, 0.5, 0.05, 0.005 nmol/mouse) dose-dependently induced potent hyperalgesic effects in the 48 °C warm-water tail-flick test in mice. I.c.v. pretreatment with N/OFQ(13–17) (5, 0.5, 0.05 nmol/mouse) potentiated the analgesic effects induced by morphine (i.p., 2 mg/kg) and reversed the hyperalgesic effects induced by N/OFQ (i.c.v., 5 nmol/mouse). The hyperalgesic effects induced by N/OFQ(13–17) could not be antagonized by [Nphe1]N/OFQ(1–13)NH2 or naloxone. These findings suggest that N/OFQ(13–17) may play important roles in pain modulation at supraspinal level in mice and elicits these effects through a novel mechanism independent of the N/OFQ receptor and the μ, δ and κ opioid receptors. [Copyright &y& Elsevier]