The nociceptin/orphanin FQ receptor antagonist, [Nphe1]NC(1-13)NH2, potentiates morphine analgesia.
Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptide/receptor system which has been implicated in the regulation of various central functions, including pain. The aim of the present study was to explore the involvement of the endogenous NC/OP4 system in the modulation of opioid analgesia using the selective OP4 receptor antagonist [Nphe1]NC(1-13)NH2. Experiments were performed in mice exposed to acute as well as chronic treatment with morphine. [Nphe1]NC(1-13)NH2, injected i.c.v. at 30 nmol, strongly potentiated the analgesic effect of supraspinal morphine (1 nmol, i.c.v.) while it only slightly increased the antinociceptive activity of morphine given systemically (5 mg/kg, s.c.). [Nphe1]NC(1-13)NH, (30 nmol, i.c.v.) also potentiated morphine analgesia in mice made tolerant to the opiate (30 mg/kg/day for 4 days). These findings implicate the endogenous NC signaling as a modulator of morphine analgesia and tolerance.
Rizzi
A
A
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Bigoni
R
R
Marzola
G
G
Guerrini
R
R
Salvadori
S
S
Regoli
D
D
Calo
G
G
D000698:Analgesia; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D004361:Drug Tolerance / Q000502:physiology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009020:Morphine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722287:Oprl1 protein, mouse