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


METHODS
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.


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.


CONCLUSIONS
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.
Croci
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T
Research Center Sanofi-Midy, Exploratory Research Department, Sanofi-aventis S.p.A., Milan, Italy. tiziano.croci@sanofi-aventis.com
Zarini
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E
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D005260:Female; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D007596:Joints / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013997:Time Factors; D014110:Touch
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D000077285:Rimonabant