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.