Many reports have shown the efficacy of cannabinoid agonists in chronic pain, whereas no report exists concerning the potential effect of cannabinoid antagonists following prolonged treatment. We tested the effects of repeated administration of the selective cannabinoid receptor type 1 (CB1) antagonist, SR141716 (rimonabant), in rats with chronic constriction injury of the sciatic nerve (CCI), an animal model of neuropathic pain. The repeated oral administration of SR141716 (1, 3 and 10 mg/kg, once a day for 1 week, from day 7 after the injury) dose dependently attenuated both thermal and mechanical hyperalgesia. A similar effect was observed in CCI wild-type mice, whereas SR141716 was unable to elicit pain relief in CB1 knockout mice, suggesting CB1 receptors involvement in the SR141716-induced antihyperalgesia. The antihyperalgesic activity of SR141716 was associated with a significant reduction of several pro-inflammatory and pro-nociceptive mediators such as tumor necrosis factor alpha (TNFalpha), prostaglandin-E2 (PGE2), lipoperoxide and nitric oxide (NO) levels. The histological analysis of sciatic nerve sections showed a marked degeneration of myelinated fibers in CCI rats, which was substantially reduced after repeated administration of SR141716. This suggests that the compound may favour myelin repair and consequently promote long-lasting functional recovery. This was confirmed by the maintenance of recovery for at least four weeks after treatment discontinuation. In conclusion, the present findings suggest that SR141716 is effective not only in alleviating neuropathic pain but also in favouring the nerve myelin repair.

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 dietinduced 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 À1 , 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 CFAinduced 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.

Filler materials for medical use present limits, such as the induction of chronic inflammation and fibrosis. In the search for synthetic materials with improved biocompatible properties, a new polyacrylamide hydrogel, Aquamid (Contura SA, Montreux, Switzerland), has been investigated in preclinical systems. In cell cultures (endothelial cells and fibroblast), no or only transient biological effects were associated with 10% Aquamid exposure. The Aquamid-host interactions were examined in mice (10 mice per group) implanted subcutaneously or in the mammary fat pad with a very large volume (1.5 ml) of the material. Blood analysis, performed after 15 and 94 days (five mice per time for each group) to detect acute or late manifestations of toxicity, did not reveal relevant abnormalities in either group of Aquamid-bearing mice compared with control mice, except for a transient thrombocytopenia and a mild leukocytosis. Histological analysis of the pellet showed the presence of a thin, poorly vascularized cyst wall in implants. Only mild mesenchymal reparative and inflammatory processes were observed, even at longer observation times (more than 400 days). No alterations in any organ were detected. Despite the large volume implanted (approximately 5 percent of mouse body weight), the Aquamid pellet maintained its original size and shape without spreading or sticking to surrounding tissues. In conclusion, the study indicated a good tolerability of the new biopolymer in preclinical systems. The clinical utility of this new compound, if confirmed by clinical randomized trials showing its atoxic properties, could be in the field of aesthetic plastic surgery as a filler material for body contouring and in reconstructive surgery and above all in cancer patients to restore surgical defects.