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CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain

Clayton, N.a,b; Marshall, F. H.c; Bountra, C.a,b; O'Shaughnessy, C. T.c,∗

doi: 10.1016/S0304-3959(01)00454-7
Article

The cannabinoid agonist, HU210 has been evaluated in vivo in nociceptive and inflammatory pain models in the rat. The ED50 for the anti-nociceptive (increasing mechanical withdrawal threshold) effect was 0.1 mg/kg−1 i.p., and for anti-hypersensitivity and anti-inflammatory activity was 5 μg/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 μg/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 μg/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)−1H-indole (GW405833) inhibited the hypersensitivity and was anti-inflammatory in vivo. These effects were blocked by SR144528. These findings suggest that CB1 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.

a Department of Neurology, GlaxoWellcome Research and Development Ltd, Gunnels Wood Road, Stevenage SG1 2NY, UK

b Department of Rheumatology, GlaxoWellcome Research and Development Ltd, Gunnels Wood Road, Stevenage SG1 2NY, UK

c Department of 7TM Receptors, GlaxoWellcome Research and Development Ltd, Gunnels Wood Road, Stevenage SG1 2NY, UK

Corresponding author.

Received 1 March 2001; received in revised form 12 October 2001; accepted 23 October 2001.

© 2002 Lippincott Williams & Wilkins, Inc.
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