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-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims). High severity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that was partially antagonized by naloxone, completely blocked by NC and potentiated by [Nphe1]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.
Rizzi
A
A
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara 17, 41100 Ferrara, Italy.
Marzola
G
G
Bigoni
R
R
Guerrini
R
R
Salvadori
S
S
Mogil
J S
JS
Regoli
D
D
Calò
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; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013550:Swimming / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C000722287:Oprl1 protein, mouse