Effect of the cannabinoid CB1 receptor antagonist rimonabant on nociceptive responses and adjuvant-induced arthritis in obese and lean rats

Authors


Research Center Sanofi-Midy, Exploratory Research Department, Sanofi-aventis S.p.A., Via G.B. Piranesi 38, Milan 20137, Italy. E-mail: tiziano.croci@sanofi-aventis.com

Abstract

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 CB1 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

Ancillary