Involvement of endogenous opioid systems in nociceptin-induced spinal antinociception in rats.
The present study investigates the involvement of opioid receptors in the antinociceptive effects of nociceptin in the spinal cord of the rat. Intrathecal administrations of 5 and 10 nmol of nociceptin significantly increase the withdraw response latencies to noxious thermal and mechanical stimulations. This nociceptin-induced antinociceptive effect is significantly attenuated by intrathecal injection of (Nphe(1))nociceptin(1-13)-NH(2), a selective antagonist of the nociceptin receptor (opioid receptor-like receptor ORL1), indicating an ORL1 receptor-mediated mechanism. This antinociceptive effect is also significantly attenuated by intrathecal injections of naloxone (a nonselective opioid receptor antagonist), naltrindole (a selective delta-opioid receptor antagonist), and beta-funaltrexamine (a selective mu-opioid receptor antagonist) in a dose-dependent manner, but not by the selective kappa-opioid receptor antagonist norbinaltorphimine. Since it is unlikely that nociceptin acts by direct binding to opioid receptors, these results suggest a possible interaction between the nociceptin/ORL1 and opioid systems in the dorsal horn of the rat spinal cord.
Department of Anesthesia and Perioperative Care, University of California, Box 0464, Room S-455 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Long-Chuan
LC
Yu
Jiang-Teng
JT
Lu
Yan-Hua
YH
Huang
Thomas
T
Meuser
Christian
C
Pietruck
Anja
A
Gabriel
Stefan
S
Grond
Pamela
P
Pierce Palmer
D000818:Animals; D004723:Endorphins / Q000502:physiology*; D006614:Hindlimb / Q000187:drug effects; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D000097629:Nociceptin
D004723:Endorphins; D009270:Naloxone; D009271:Naltrexone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D000097629:Nociceptin; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C051844:norbinaltorphimine; C024524:beta-funaltrexamine; C055382:naltrindole