Antagonistic effect of orphanin FQ on opioid analgesia in rat.
OBJECTIVE
To study the effect of orphanin FQ (OFQ), a newly discovered heptadecapeptide, on nociception and opioid analgesia.


METHODS
The intracerebroventricular (i.c.v.) and intrathecal (i.t.h.) injections were used to give the drugs. The tail-flick model of rats were used to test the pain threshold.


RESULTS
OFQ (i.c.v. or i.t.h.) 0.1 microgram had no effect on nociception but 0.5-10 micrograms induces hyper-reaction of rat to noxious electric stimulus; the decapeptide (OFQ1-10 i.c.v.), a fragment of the OFQ, did not affect the pain reaction of rats. Fentanyl (1 microgram, i.c.v. or i.t.h.), a selective mu-receptor agonist, DSLET (5 micrograms, i.c.v. or i.t.h.), a selective delta-receptor agonist, or U50488H (1 microgram, i.t.h.), a kappa-receptor agonist, induced an increase in pain threshold, when OFQ (0.1 or 1 microgram) was added together with one of them (except for the ith injection of DSLET), the increase of pain threshold was reduced obviously.


CONCLUSIONS
OFQ induces hyperalgesia and antagonizes opioid analgesia mediated by mu- and delta-receptors in the brain and by mu- and kappa- but not delta-receptors in the spinal cord of rats.
Zhu
C B
CB
State Key Laboratory of Medical Neurobiology, Department of Neurobiology, Shanghai Medical University, China.
Zhang
X L
XL
Xu
S F
SF
Cao
X D
XD
Wu
G C
GC
Li
M Y
MY
Cui
D F
DF
Qi
Z W
ZW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000037:antagonists & inhibitors; D000698:Analgesia; D000700:Analgesics / Q000037:antagonists & inhibitors; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors; D000818:Animals; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005283:Fentanyl / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics; D000701:Analgesics, Opioid; D004743:Enkephalin, Leucine; D005283:Fentanyl; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-