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PAIN MEDICINE

Antinociception with Intrathecal -Methyl-5-Hydroxytryptamine, a 5-Hydroxytryptamine_2A/2C Receptor Agonist, in Two Rat Models of Sustained Pain

Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan

Address correspondence and reprint request to Hideaki Obata, MD, Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi 371–8511, Japan. Address e-mail to hobata{at}showa.gunma-u.ac.jp

Type 2 serotonin (5-hydroxytryptamine [5-HT]₂) receptors in the spinal cord have been reported to mediate antinociception using pain threshold tests, but little is known about the actions of spinal 5-HT₂ receptors in sustained pain. In rats, we examined antinociceptive effects of the intrathecal administration of a 5-HT_2A/2C receptor agonist, -methyl-5-HT maleate (-m-5-HT), using the formalin test and the chronic constriction injury (CCI) model. An intrathecal catheter was implanted for injection of drugs. In the formalin test, flinches were counted from Minute 1 to 2 and Minute 5 to 6 (Phase 1) and then for 1-min periods at 5-min intervals from 10 to 60 min (Phase 2). In rats with CCI, hind paw withdrawal latency after thermal stimulation was measured. In the formalin test, intrathecal administration of -m-5-HT (1 to 100 µg) dose-dependently suppressed the number of flinches in both Phases 1 and 2. In the CCI model, intrathecally administered -m-5-HT (10 to 100 µg) attenuated thermal hyperalgesia in a dose-dependent manner. These effects were reversed by intrathecal pretreatment with a 5-HT_2A/2C antagonist, ketanserin (30 µg), or a muscarinic receptor antagonist, atropine (30 µg). These findings suggest that spinal 5-HT_2A/2C receptors mediate antinociception in inflammatory pain and neuropathic pain, and the muscarinic receptors contribute to this action.

IMPLICATIONS: Activation of spinal 5-hydroxytryptamine_2A/2C receptors mediate antinociception in rat-sustained pain models such as inflammatory pain and neuropathic pain, and spinal muscarinic receptors are involved in this action.

This article has been cited by other articles:

				B. D. Schlag, Z. Lou, M. Fennell, and J. Dunlop Ligand Dependency of 5-Hydroxytryptamine 2C Receptor Internalization J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 865 - 870. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999