对乙酰氨基酚联合曲马多腹腔注射对神经病理性疼痛大鼠的协同治疗作用

Synergic antinociceptive interaction between tramadol and acetaminophen after intraperitoneal administration in the spinal nerve ligation model of neuropathic pain

目的观察腹腔注射对乙酰氨基酚加曲马多对脊神经部分结扎大鼠神经病理性疼痛的作用。方法雄性SD大鼠建立脊神经部分结扎神经病理性疼痛后,随机分为十组(n=8):对乙酰氨基酚40mg/kg(Ⅰ组)、80mg/kg(Ⅱ组)和160mg/kg(Ⅲ组),曲马多5mg/kg(Ⅳ组)、10mg/kg(Ⅴ组)和20mg/kg(Ⅵ组),对乙酰氨基酚40mg/kg加曲马多5mg/kg(Ⅶ组),对乙酰氨基酚80mg/kg加曲马多10mg/kg(Ⅷ组),对乙酰氨基酚160mg/kg加曲马多20mg/kg(Ⅸ组),生理盐水对照组(Ⅹ组)。采用热辐射法和vonFrey细丝法分别测定大鼠热刺激缩足反射潜伏期(TWL)和机械刺激缩足反射痛阈值(MWT)。结果与Ⅹ组相比,除Ⅰ、Ⅱ、Ⅲ、Ⅳ组大鼠TWL和MWT差异无统计学意义外,其余各组的TWL和MWT均显著延长或增大(P<0.05或P<0.01);与Ⅳ、Ⅴ、Ⅵ组相比,Ⅶ、Ⅷ、Ⅸ组的TWL和MWT均显著延长或增大(P<0.05或P<0.01)。结论腹腔注射对乙酰氨基酚加曲马多对脊神经部分结扎大鼠机械性痛觉过敏和热痛觉过敏具有协同的抗伤害感受性作用,对临床上神经病理性疼痛的治疗具有指导意义。

Objective To observe the effect of acetaminophen＋ tramadol ip. injection on the neuropathic pain induced by ligation of the L5 spinal nerve （SNL） in rats. Methods Eighty male SD rats weighing 250-320 g were anesthetized with pentobarbital 40 mg/kg and the model of unilateral spinal nerve ligation （SNL） （LS,L6） before experiment was established. The animals were randomly divided into 10 groups with 8 rats each. The rats in group Ⅰ, Ⅱ and Ⅲ were treated with acetaminophen 40 mg/kg,80 mg/kg and 160 mg/kg ip respectively. The rats in group Ⅳ, Ⅴ and Ⅵ were treated with tramadol 5 mg/kg, 10 mg/kg and 20 mg/kg respectively. The rats in group Ⅶ were given acetaminophen 40 mg/kg ＋ tramadol 5 mg/kg, in group Ⅷ acetaminophen 80 mg/kg ＋ tramadol 10 mg/kg and in group IX acetaminophen 160 mg/kg ＋ tramadol 20 mg/kg. Control group （group X ） received normal saline. Thermal withdrawal latency（TWL） and mechanical withdrawal threshold（MWT） of rats were determined by Hagreave＇s thermal radiation apparatus and yon Frey＇s method of microfilament, respectively. Results Compared with group X , TWL and MWT in the experimental groups increased significantly except group Ⅰ , Ⅱ , Ⅲ and Ⅳ （P〈0.05 or P〈0.01） ; Compared with group Ⅳ, Ⅴ and Ⅵ, TWL and MWT in group Ⅶ, Ⅷ and IX increased significantly （P〈0. 05 or P〈0. 01 ）. Conclusion The aeetaminophen-tramadol combination can interact synergistically to suppress SNL induced mechano-allodynia and heat hyperalgesia,and may represent a therapeutic advantage for clinical treatment of neuropathic pain.