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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., (Copyright 1999 Elsevier Science B.V.)

Aim: 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., Conclusion: 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.

Orphanin FQ (OFQ) is a newly discovered 17-amino-acid peptide capable of inducing hyperalgesia. In the present study, the effects of OFQ on basal pain threshold and acupuncture anlgesia (AA) in rats were observed using the tail-flick test. It was found that intrathecal (i.t.) or intracerebroventricular (i.c.v.) administrition of 0.1 microgram OFQ had no effect on basal pain threshold of rats, while 1 microgram OFQ could lower the threshold. However, OFQ at both the doses (0.1 or 1.0 microgram) administered by either i.t. or i.c.v. injection could antagonize AA with that occuring in the brain being more prominent then in the spinal cord. When the rats were repeatedly treated with antisense oligonucleotide to block synthesis of OFQ receptor, pain threshold increased significantly. At such instance, when the OFQ was combined with acupuncture, the effect of AA showed no obvious change. The above results show that the OFQ at small dose has no effect on pain threshold but can lower it at larger dose; while in both cases OFQ can antagonize AA.

The influence of orphanin FQ (OFQ) (a newly discovered 17-amino acid peptide) on acupuncture analgesia (AA) was assessed in rat tail-flick model. Intracerebroventricular (i.c.v.) injection of OFQ (1 microgram) elicited a significant decrement of pain threshold which was abolished by the repeated pretreatment with antisense oligonucleotide (ASO) to OFQ receptor. Electroacupuncture (EA) induced an obvious analgesic effect; when OFQ was used combined with EA, it showed a dose-dependent effect on antagonizing the EA analgesia. When rat was repeatedly i.c.v. injected with ASO to block the synthesis of OFQ receptor, the EA analgesia was enhanced markedly. In this instance, the OFQ did not show antagonistic effect on EA analgesia any more. The results suggest that the OFQ play its antagonistic role on EA analgesia via activating OFQ receptor.