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Anesth Analg 2007;104:719-725
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000255291.38637.26

ANALGESIA

Antinociceptive Synergy Between the Cannabinoid Receptor Agonist WIN 55,212-2 and Bupivacaine in the Rat Formalin Test

Sinyoung Kang, MD, PhD, Chi Hyo Kim, MD, PhD, Heeseung Lee, MD, Dong Yeon Kim, MD, PhD, Jong In Han, MD, PhD, Rack Kyung Chung, MD, PhD, and Guie Yong Lee, MD, PhD

From the Department of Anesthesiology and Pain Medicine, Ewha Womans University Medical College, Seoul, Korea.

Address correspondence and reprint requests to Chi Hyo Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Ewha Womans University Mokdong Hospital, 911-1 Mokdong, Yangcheon-Ku, Seoul, Korea 158-710. Address e-mail to 120060{at}mm.ewha.ac.kr.

Abstract

BACKGROUND: The analgesic interaction between cannabinoids and local anesthetics has not been investigated. We sought to determine the nature of the interaction between the intrathecal cannabinoid receptor agonist (WIN 55,212-2) and bupivacaine using the formalin test.

METHODS: Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats. After intrathecal administration of WIN 55,212-2, bupivacaine, or their combination, 50 µL of 5% formalin was injected subcutaneously into the hindpaw. Dose–response curves were established and the respective ED50 (50% effective dose) values were determined for each agent alone. Fixed-ratio combinations of WIN 55,212-2 and bupivacaine were tested for combined antinociceptive effects in the formalin test and an isobolographic analysis was performed to characterize the pharmacologic interaction of both drugs.

RESULTS: Intrathecally administered WIN 55,212-2, bupivacaine, or their combination produced a dose-dependent decrease in the number of flinches during Phase 1 and 2 of the formalin test. Isobolographic analysis revealed a synergistic interaction between intrathecal WIN 55,212-2 and bupivacaine in both phases of the formalin test. In combination, the ED50 value was significantly smaller than the theoretical additive value (P < 0.05).

CONCLUSIONS: These results demonstrate that intrathecally coadministered WIN 55,212-2 and bupivacaine provide synergistic antinociceptive interaction in both phases of the formalin test.






Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2007 by the International Anesthesia Research Society.