Effects of orphanin FQ on endomorphin-1 induced analgesia.
Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the mu-opiate receptor. In the present study, the effect of OFQ or/and endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i.c.v.) administration of OFQ (1, 5 microg) could shorten tail-flick latency; In contrast, intrathecal (i.t.) administration of OFQ (1, 2 or 10 microg) could increase the latency; i.c.v. (1, 2, 5 microg) or i.t. (0.2, 2, 5 microg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5 microg) when intraventricularly injected together with endomorphin-1 (5 microg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1 microg) intrathecally injected together with endomorphin-1 (0.2 microg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested.
Wang
Y Q
YQ
State Key Laboratory of Neurobiology, Shanghai Medical University, Shanghai, 200032, China.
Zhu
C B
CB
Wu
G C
GC
Cao
X D
XD
Wang
Y
Y
Cui
D F
DF
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C105293:endomorphin 1