河豚毒素对4种急性疼痛模型的镇痛效应比较研究

Comparative study on analgesic effect of tetrodotoxin in four acute pain models

目的评估河豚毒素(tetrodotoxin,TTX)对4种急性疼痛模型的镇痛效果,为其合理应用提供实验支持。方法动物肌内注射1 mg/kg盐酸吗啡或不同剂量TTX,TTX剂量为0、0.5、1、2、4、8μg/kg,给药后40 min,分别进行醋酸扭体实验、福尔马林刺激实验、热板实验和甩尾实验,记录动物疼痛反应或痛阈,计算疼痛抑制率;取动物血清,Elisa法测定花生四烯酸含量。结果盐酸吗啡对4种急性疼痛模型均有显著镇痛效应;TTX可减少醋酸诱导的小鼠扭体次数,降低福尔马林诱导的大鼠Ⅰ相和Ⅱ相疼痛反应,对两种疼痛模型的最高疼痛抑制率均达到80.00%以上;TTX在甩尾实验和热板实验中有一定的镇痛作用,最高疼痛抑制率分别为25.00%、19.79%。醋酸和福尔马林均能导致动物血清花生四烯酸升高,但是TTX对花生四烯酸无显著抑制作用。结论 TTX对醋酸和福尔马林诱导的化学性刺激疼痛模型具有良好的镇痛效果,而对热诱导(热板和热水)的物理性刺激疼痛模型的镇痛效果较弱,TTX可能通过阻断炎性介质介导的疼痛反应产生镇痛效果。

Objective To evaluate the analgesic effect of tetrodotoxin(TTX) in four types of acute pain models and provide experimental support for its rational application. Methods Mice or rats were intramuscularly pretreated with morphine(1 mg/kg) or TTX(0, 0.5, 1, 2, 4 and 8 μg/kg) 40 min before acetic acid writhing test, formalin stimulation test, hot plate test or tail flick test. Pain response or pain threshold were recorded, and inhibition rate was calculated during the tests. The arachidonic acid of serum was determined by Elisa. Results Significant analgesic effects were observed with morphine in all four acute pain models.TTX dose-dependently reduced the number of writhing induced by acetic acid and inhibited the pain response induced by formalin during phase Ⅰ and phase Ⅱ, with the highest inhibition rate of more than 80.00% in two pain models. TTX showed analgesic effect in tail flick test and hot plate test, with the highest inhibition rate of 25.00% and 19.79%, respectively. Both acetic acid and formalin increased arachidonic acid in animal serum, but TTX had no significant inhibitory effect on the releasing of arachidonic acid.Conclusion TTX showed significant analgesic effect in the chemical stimulation pain models induced by acetic acid and formalin,but limited analgesic effect was observed on the physical stimulation pain model induced by heat(hot plate and hot water). TTX may produce analgesic effect by blocking the inflammatory mediators mediating pain response.