Suppression of complete freund's adjuvant-induced adjuvant arthritis by cobratoxin

Abstract

Aim:Cobratoxin (CTX), the long-chain α-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats.Methods:Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results:CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-α, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 g/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-α, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc).Conclusion:These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX. © 2009 CPS and SIMM.