Antinociceptive synergy between the cannabinoid receptor agonist WIN 55,212-2 and bupivacaine in the rat formalin test

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)719-725
Number of pages7
JournalAnesthesia and Analgesia
Volume104
Issue number3
DOIs
StatePublished - Mar 2007

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