PMID- 19169271 OWN - NLM STAT- MEDLINE DCOM- 20090428 LR - 20240502 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 30 IP - 2 DP - 2009 Feb TI - Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin. PG - 219-27 LID - 10.1038/aps.2008.20 [doi] AB - AIM: Cobratoxin (CTX), the long-chain alpha-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-alpha (TNF-alpha), 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 alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). RESULTS: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, 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 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, 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. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX. FAU - Liu, Yan-Li AU - Liu YL AD - College of Pharmacy, Soochow University, Suzhou, China. FAU - Lin, Hai-Ming AU - Lin HM FAU - Zou, Rong AU - Zou R FAU - Wu, Jun-Chao AU - Wu JC FAU - Han, Rong AU - Han R FAU - Raymond, Laurence N AU - Raymond LN FAU - Reid, Paul F AU - Reid PF FAU - Qin, Zheng-Hong AU - Qin ZH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090126 PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 0 (Analgesics) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cobra Neurotoxin Proteins) RN - 0 (Interleukin-1) RN - 0 (Interleukin-2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 9007-81-2 (Freund's Adjuvant) SB - IM MH - Analgesics/*therapeutic use MH - Animals MH - Anti-Inflammatory Agents/*therapeutic use MH - Arthritis, Experimental/*drug therapy/immunology/pathology/physiopathology MH - Behavior, Animal/physiology MH - Cobra Neurotoxin Proteins/*therapeutic use MH - Freund's Adjuvant/*immunology MH - Humans MH - Interleukin-1/metabolism MH - Interleukin-10/metabolism MH - Interleukin-2/metabolism MH - Male MH - Pain Measurement MH - Rats MH - Rats, Sprague-Dawley MH - Synovial Membrane/cytology/pathology MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC4002463 EDAT- 2009/01/27 09:00 MHDA- 2009/04/29 09:00 PMCR- 2009/02/01 CRDT- 2009/01/27 09:00 PHST- 2009/01/27 09:00 [entrez] PHST- 2009/01/27 09:00 [pubmed] PHST- 2009/04/29 09:00 [medline] PHST- 2009/02/01 00:00 [pmc-release] AID - aps200820 [pii] AID - 10.1038/aps.2008.20 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2009 Feb;30(2):219-27. doi: 10.1038/aps.2008.20. Epub 2009 Jan 26.