Journal
PAIN
Volume 96, Issue 3, Pages 253-260Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/S0304-3959(01)00454-7
Keywords
CB1; CB2; cannabinoid receptors; inflammatory pain
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The cannabinoid agonist, HU210 has been evaluated in vivo in nociceptive and inflammatory pain models in the rat. The ED50 for the antinociceptive (increasing mechanical withdrawal threshold) effect was 0.1 mg/kg - (1)i.p., and for anti-hypersensitivity and anti-inflammatory activity was 5 mug/kg - (1)i.p. (in the carrageenan model). The selective CB1 antagonist, AM281 (0.5 mg/kg - (1)i.p.) reversed effects of HU210 (10 and 30 mug/kg - (1)i.p.) in both nociceptive and inflammatory models of hypersensitivity. The selective CB2 antagonist, SR144528 (1 mg/kg - (1)i.p.) antagonised effects of HU210 (30 mug/kg - (1)i.p.) in the carrageenan induced inflammatory hypersensitivity. The CB2 agonist, 1-(2,3-Dichlorobenzoyl)-5-methoxy-2-methyl-(2-(morpholin-4-yl)ethyl) - H-1-indole (GW405833) inhibited the hypersensitivity and was anti-inflammatory in vivo. These effects were blocked by SR144528. These findings suggest that CBI receptors are involved in nociceptive pain and that both CB1 and CB2 receptors are involved in inflammatory hypersensitivity. Future studies will investigate effects on identified inflammatory cells within the inflamed tissue to further elucidate the role of cannabinoid receptors. (C) 2002 Published by Elsevier Science B.V. on behalf of International Association for the Study of Pain.
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