Acta Pharmacologica Sinica (2009) 30: 219-227; doi: 10.1038/aps.2008.20; published online 26th January 2009

Suppression of complete Freund’s adjuvant-induced adjuvant arthritis by cobratoxin

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 µg/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.

Keywords: cobratoxin; adjuvant arthritis; anti-inflammatory; anti-nociception; α7-nicotinic acetylcholine receptor