氢溴酸高乌甲素注射液对手术致痛大鼠脊髓Fos蛋白及疼痛反应的影响

Effect of lappaconitine hydrobromide injection on Fos protein expression in spinal cord and incisional pain in rats

目的探讨氢溴酸高乌甲素注射液对手术致痛大鼠脊髓Fos蛋白表达及疼痛反应的影响。方法按Brennan法手术建立Sprague-Dawley大鼠手术切口疼痛模型。48只大鼠随机分为6组,每组各8只:对照组术前16min腹腔注射0.9%氯化钠溶液;术前低剂量高乌甲素组、术前中剂量高乌甲素组和术前高剂量高乌甲素组均于术前16min分别腹腔注射氢溴酸高乌甲素注射液1、2和4mg/kg;术后高乌甲素组于术后16min腹腔注射氢溴酸高乌甲素注射液4mg/kg;去甲肾上腺素(NE)生成减少组于术前2h腹腔注射二乙基二硫代氨基甲酸钠200mg/kg+术前16min腹腔注射4mg/kg氢溴酸高乌甲素注射液。采用术后大鼠1h累积疼痛评分进行疼痛行为观察,免疫组织化学方法进行脊髓背角Fos蛋白免疫反应阳性神经元(FLIN)计数。结果术前低剂量高乌甲素组、术前中剂量高乌甲素、术前高剂量高乌甲素组和术后高乌甲素组脊髓背角FLIN计数和疼痛累积评分均显著低于对照组(P值均<0.05),术前中剂量高乌甲素组显著低于术前低剂量高乌甲素组(P值均<0.05),术前高剂量高乌甲素组显著低于术前中剂量高乌甲素组、术前低剂量高乌甲素组、术后高剂量高乌甲素组和NE生成减少组(P值分别<0.05、0.01)。结论氢溴酸高乌甲素注射液腹腔注射可抑制手术致痛大鼠的脊髓背角Fos蛋白的表达以及疼痛反应,并呈量效关系,预先给药较术后给药的镇痛效果好。氢溴酸高乌甲素注射液可能通过促进中枢NE的释放,加强脑干下行调制系统,抑制外周伤害性刺激在脊髓水平的传入而达到镇痛作用。

Objective To investigate the effect of lappaconitine hydrobromide injection on Fos-protein expression of spinal cord and pain reaction induced by surgical incision in rats. Methods Sprague-Dawley rat model of incisional pain was made according to Brennan method and 48 animals were randomly invided into six groups. Normal saline was intraperitoneally injected 16 mins before incision in control group. Lappaconitine hydrobromide injection （1, 2 and and 4 mg/kg 16 mins after incision） was administered. Sodium diethyl dithiocarbamate （DDC 200 mg/kg） was intraperitoneally injected 2 h before surgery and lappaconitine hydrobromide injection （4 mg/kg） was infused 16 mins before incision in DDC group. The pain was evaluated by behavioral study after surgery. FLIN expression in the dorsal horn were observed by immunohistology. Results FLIN and pain scoring in the four lappaconitine groups were significantly lower than those in the control group （all P〈0.05）. FLIN and pain scoring in the rats with 2 mg/kg lappaconitine before incision were significantly lower than those in the rats with 1 mg/kg lappaconitine before incision （both P〈0.05）. FLIN and pain scoring in the rats with 4 mg/kg lappaconitine before incision were significantly lower than those in the rats with 2 mg/kg lappaconitine before incision （both P〈0.05）, 4 mg/kg lappaconitine after incision （both P〈0.01） and DDC application （both P〈0.01）. Conclusion Fos protein expression in dorsal horn of spinal cord and pain reaction can be suppressed by intraperitoneal injection of lappaconitione in a dose-dependent manner in rats. The analgesic effect of lappaconitione given before incision is better than those given after incision. Lappaconitine hydrobromide may reinforce the activity of pain modulation system in brainstem and inhibit the inputs of peripheral pain message through enhancing norepinephrine releasing.