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NEUROPHARMACOLOGY

Buprenorphine Activates µ and Opioid Receptor Like-1 Receptors Simultaneously, but the Analgesic Effect Is Mainly Mediated by µ Receptor Activation in the Rat Formalin Test

Department of Anesthesiology, Graduate School of Medicine, Chiba University, Chiba, Japan

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 µ 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 µl of 5% formalin) induces biphasic flinching (phase 1, 0-6 min; phase 2, 10-60 min) of the injected paw. Buprenorphine, naloxone (a µ-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 µ and ORL1 receptors. The analgesic effect of systemically administered buprenorphine was suppressed by the concomitant activation of supraspinal ORL1 receptor.

Address correspondence to: Dr. Tatsuo Yamamoto, Department of Anesthesiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260, Japan. E-mail: yamamotot{at}faculty.chiba-u.jp

This article has been cited by other articles:

				M. S. Virk, S. Arttamangkul, W. T. Birdsong, and J. T. Williams Buprenorphine Is a Weak Partial Agonist That Inhibits Opioid Receptor Desensitization J. Neurosci., June 3, 2009; 29(22): 7341 - 7348. [Abstract] [Full Text] [PDF]