PMID:16565164

Citation	Yamamoto, T, Shono, K and Tanabe, S (2006) Buprenorphine activates mu and opioid receptor like-1 receptors simultaneously, but the analgesic effect is mainly mediated by mu receptor activation in the rat formalin test. J. Pharmacol. Exp. Ther. 318:206-13
Abstract	Buprenorphine is a mixed opioid receptor agonist-antagonist. Recently, buprenorphine was reported to act as an agonist to opioid receptor like-1 (ORL1) receptor. In the present study, we examined the role of spinal and supraspinal mu receptors and spinal and supraspinal ORL1 receptors in producing an analgesic effect by intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. administration of buprenorphine in the rat formalin test. Male rats were prepared with i.t. catheters or i.c.v. injection cannulas. The paw formalin injection (50 microl of 5% formalin) induces biphasic flinching (phase 1, 0-6 min; phase 2, 10-60 min) of the injected paw. Buprenorphine, naloxone (a mu-opioid receptor antagonist), or (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J113397) (an ORL1 receptor-selective antagonist) was administered i.t., i.c.v., or i.p.. Intrathecal, i.c.v., or i.p. injection of buprenorphine produces an analgesic effect in a dose-dependent manner. The effect of i.c.v. buprenorphine was antagonized by i.c.v. naloxone or i.c.v. J113397, and the effect of i.t. buprenorphine was antagonized by i.t. naloxone or i.t. J113397. The effect of i.p. buprenorphine was antagonized by i.p. or i.t. naloxone but not by i.c.v. naloxone. The analgesic effect of i.p. buprenorphine was enhanced by i.p. J113397 or i.c.v. J113397. Intraperitoneal, but not i.t. or i.c.v., buprenorphine decreased the number of Fos-like immunoreactivity positive neurons in the L4-L5 spinal dorsal horn. These data indicated that buprenorphine affects nociceptive processing by acting at both supraspinal and spinal mu and ORL1 receptors. The analgesic effect of systemically administered buprenorphine was suppressed by the concomitant activation of supraspinal ORL1 receptor.
Links	PubMed Online version:10.1124/jpet.105.100859
Keywords	Analgesics, Opioid/pharmacology; Animals; Buprenorphine/pharmacology; Male; Narcotic Antagonists; Pain Measurement/drug effects; Pain Measurement/methods; Rats; Rats, Sprague-Dawley; Receptors, Opioid/agonists; Receptors, Opioid/metabolism; Receptors, Opioid, mu/agonists; Receptors, Opioid, mu/antagonists & inhibitors; Receptors, Opioid, mu/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:OPRM	involved_in	GO:0051930: regulation of sensory perception of pain	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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