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Effect of the cannabinoid CB 1 receptor antagonist rimonabant on nociceptive responses and adjuvant‐induced arthritis in obese and lean rats
Author(s) -
Croci T,
Zarini E
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707138
Subject(s) - rimonabant , medicine , arthritis , hyperalgesia , allodynia , cannabinoid receptor antagonist , cannabinoid receptor , nociception , antagonist , endocrinology , inflammatory arthritis , cannabinoid , pharmacology , receptor
Background and purpose: Obesity is a risk factor for several inflammation‐based diseases including arthritis. We investigated the anti‐nociceptive and anti‐inflammatory effects of the cannabinoid CB 1 receptor antagonist rimonabant in lean and diet‐induced obese female rats with arthritis induced by complete Freund's adjuvant (CFA) injected in the right hind‐paw. Experimental approach: The effect of oral rimonabant was assessed in rat paws on thermal hyperalgesia, mechanical allodynia, oedema, global arthritis score, nitrite/nitrate levels and ankle widths. Key results: After 7 but not after 14 days, the inflammatory response to CFA was significantly higher in obese than lean rats; however, the nociceptive response (thermal hyperalgesia and mechanical allodynia) was similar. Oral rimonabant (3 or 10 mg kg −1 , once a day for 1 week from day 7 after CFA) only reduced the global arthritic score and joint width in obese rats, with no effect on the paw oedema. It also markedly reduced thermal hyperalgesia and mechanical allodynia in both lean and obese rats, with a greater effect in the latter. Conclusion and implications: Rimonabant appears to be a potent inhibitor of sensorial hypersensitivity associated with CFA‐induced arthritis in obese rats, in which the inflammatory reaction is more severe than in lean rats. It may thus have therapeutic potential in obesity‐associated inflammatory diseases, particularly in the treatment of the pain associated with arthritis. British Journal of Pharmacology (2007) 150 , 559–566. doi: 10.1038/sj.bjp.0707138