CB₂ cannabinoid receptor mediation of antinociception

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• 作者：Mohab M. Ibrahim ; Megan L. Rude ; Nicola J. Stagg ; Heriberto P. Mata ; Josephine Lai ; Todd W. Vanderah ; Frank Porreca ; Nancy E. Buckley ; Alexandros Makriyannis and T. Philip Malan ; Jr.
• 关键词：Cannabinoid ; CB₂ ; Pain ; Nociception ; Knockout ; AM1241 ; WIN55 ; 212-2
• 刊名：Pain
• 出版年：2006
• 出版时间：May 2006
• 年：2006
• 卷：122
• 期：1-2
• 页码：36-42
• 全文大小：145 K

文摘

Management of acute pain remains a significant clinical problem. In preclinical studies, CB₂ cannabinoid receptor-selective agonists inhibit nociception without producing central nervous system side effects. The CB₂ receptor-selective agonist AM1241 produces antinociceptive effects that are antagonized by CB₂, but not CB₁, receptor-selective antagonists, suggesting that activation of CB₂ receptors results in antinociception. However, it has not been possible to definitively demonstrate that these effects are mediated by CB₂ receptors, because we have lacked the pharmacological tools to confirm the in vivo receptor selectivity of the antagonists used. Further, recent evidence for cannabinoid-like receptors beyond CB₁ and CB₂ raises the possibility that AM1241 exerts its antinociceptive effects at uncharacterized CB₂-like receptors that are also inhibited by AM630. The experiments reported here further test the hypothesis that CB₂ receptor activation inhibits nociception. They evaluated the antinociceptive actions of AM1241 and the less-selective CB₂ receptor agonist WIN55,212-2 in wild-type mice and in mice with genetic disruption of the CB₂ receptor ( mice). AM1241 inhibited thermal nociception in mice, but had no effect in littermates. WIN55,212-2 produced equivalent antinociception in and mice, while its antinociceptive effects were reduced in compared to mice. The effects of morphine were not altered in compared to mice. These data strongly suggest that AM1241 produces antinociception in vivo by activating CB₂ cannabinoid receptors. Further, they confirm the potential therapeutic relevance of CB₂ cannabinoid receptors for the treatment of acute pain.