Department of Pharmacology, Soochow University School of Pharmacy, Suzhou, China.
Acta Pharmacol Sin. 2011 Oct;32(10):1233-8. doi: 10.1038/aps.2011.65. Epub 2011 Aug 15.
To investigate the analgesic effect of cobratoxin (CTX), a long-chain α-neurotoxin from Thailand cobra venom, in a rat model of formalin-induced inflammatory pain.
Inflammatory pain was induced in SD rats via injecting 5% formalin (50 μL) into the plantar surface of their right hind paw. CTX and other agents were ip administered before formalin injection. The time that the animals spent for licking the injected paw was counted every 5 min for 1 h.
CTX (25, 34, and 45 μg/kg) exhibited a dose-dependent analgesic effect during the phase 1 (0-15 min) and phase 2 (20-60 min) response induced by formalin. Pretreatment with naloxone (0.5 or 2.5 mg/kg) did not block the analgesic effect of CTX. Pretreatment with atropine at 5 mg/kg, but not at 2.5 mg/kg, antagonized the analgesic effect of CTX. Treatment with the nonselective nAChR antagonist mecamylamine (3 mg/kg) inhibited the analgesic effects of CTX in Phase 1 and Phase 2 responses, while with the selective α7-nAChR antagonist methyllycaconitine (3 mg/kg) antagonized the effect of CTX only in the Phase 1 response. Treatment with the α7-nAChR agonist PNU282987 (3 mg/kg) significantly reduced the formalin-induced phase 2 pain response, but only slightly reduced the Phase 1 pain response.
The results suggest that CTX exerts an antinociceptive effect in formalin-induced inflammatory pain, which appears to be mediated by mAChR and α7-nAChR.
研究来自泰国眼镜蛇毒液的长链α神经毒素 cobratoxin（CTX）在福尔马林诱导的炎症性疼痛大鼠模型中的镇痛作用。
通过向 SD 大鼠右后足底表面注射 5%福尔马林（50μL）诱导炎症性疼痛。在注射福尔马林之前，通过腹腔内给药 CTX 和其他试剂。在 1 小时内，每 5 分钟记录动物舔注射爪的时间。
CTX（25、34 和 45μg/kg）在福尔马林诱导的第 1 期（0-15 分钟）和第 2 期（20-60 分钟）反应中表现出剂量依赖性的镇痛作用。纳洛酮（0.5 或 2.5mg/kg）预处理不能阻断 CTX 的镇痛作用。阿托品（5mg/kg）预处理，但 2.5mg/kg 预处理不能拮抗 CTX 的镇痛作用。非选择性烟碱型乙酰胆碱受体拮抗剂美卡拉明（3mg/kg）抑制 CTX 在第 1 期和第 2 期反应中的镇痛作用，而选择性α7 烟碱型乙酰胆碱受体拮抗剂甲基六氢吡啶（3mg/kg）仅拮抗 CTX 在第 1 期反应中的作用。α7 烟碱型乙酰胆碱受体激动剂 PNU282987（3mg/kg）处理显著降低了福尔马林诱导的第 2 期疼痛反应，但仅略微降低了第 1 期疼痛反应。
结果表明 CTX 在福尔马林诱导的炎症性疼痛中表现出镇痛作用，这似乎是通过 mAChR 和α7-nAChR 介导的。
