目的观察坐骨神经局部反复(慢性)注射阿米替林和布比卡因对慢性坐骨神经结扎损伤(chronic constriction injury,CCI)大鼠机械和热痛阈的影响,及神经组织病理学的改变,探讨其对外周抗痛觉过敏作用及神经组织的影响。方法健康成年雄性SD大鼠24只,体重(200±20)g,按照Bennett等的方法制备CCI模型,5d后随机分为3组(n=8):阿米替林组(A组)、布比卡因组(B组)、生理盐水组(C组)。模型制备后5、7、9d分别经留置导管给予0.5mL的0.5%阿米替林、0.5%布比卡因及生理盐水。观察大鼠一般情况,根据Hwang等标准行运动功能评分;于注药前及第3次注药后1、3、5、7d测定机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩腿反射潜伏期(thermal withdrawal latency,TWL)。于模型制备后16d取坐骨神经标本,行大体观察及组织学观察,采用Estebe评分方法行组织学评分。结果大鼠均存活至行为学实验观察完成。A、B组大鼠于每次注药后均出现不同程度运动障碍,A组在8h内、B组在2h内运动功能评分与C组和注药前比较差异均有统计学意义(P<0.05);但第3次注药A组在8h后、B组在2h后大鼠运动功能均完全恢复。A组第3次注药完成后1、3d的MWT和TWL较注药前及注药后5、7d显著升高,也较1、3d的B、C组显著升高,差异均有统计学意义(P<0.05);B组各时间点MWT和TWL与注药前及C组比较差异均无统计学意义(P>0.05)。3组大鼠坐骨神经光镜下组织学观察可见神经外膜、神经束膜完整,轴索排列大致整齐,无明显脱髓鞘改变,少量炎性细胞浸润,各组坐骨神经组织学评分均为1分,差异无统计学意义(P>0.05)。结论坐骨神经局部反复(慢性)注射0.5%阿米替林对神经病理性疼痛大鼠具有外周抗痛觉过敏的作用,其作用具有累加效应,且未见坐骨神经发生明显病理学改变。 Objective To observe the effects of local repeated (chronic) injection of amitriptyline and bupivacaine on the mechanical and thermal pain thresholds of chronic constriction injury (CCI) rats and the histopathological changes of the nerve in the sciatic nerve. Week anti-hyperalgesia and neural tissue effects. Methods Twenty-four healthy male Sprague-Dawley rats weighing 200 ± 20 g were used to prepare CCI model according to the method of Bennett et al. They were randomly divided into three groups (n = 8): Amitriptyline (group A) Bupivacaine group (group B), saline group (group C). 0.5 mL of 0.5% amitriptyline, 0.5% bupivacaine and saline were given via indwelling catheter on the 5th, 7th and 9th day after model preparation. The general condition of the rats was observed and motor function scores were evaluated according to the standard of Hwang. Mechanical withdrawal threshold (MWT) and heat shrinkage were measured at 1, 3, 5 and 7 days after the third and third injection, Thermal withdrawal latency (TWL). Sciatic nerve specimens were obtained 16 days after model preparation. Gross observation and histological observation were performed. The histological score was calculated by Estebe score method. Results All rats survived until the behavioral experiment was completed. Rats in groups A and B showed varying degrees of dyskinesia after each injection. Within 8 hours in group A, the scores of motor function in group B within 2 hours were significantly different from those in groups C and before injection (P < 0.05). However, in the third injection group A, the motor function of rats in group B recovered completely after 2 hours. The MWT and TWL at 1 and 3 days after the third injection in group A were significantly higher than those before injection and 5 and 7 days after injection, and also significantly higher than those in groups B and C at 1 and 3 days (P <0.05). There was no significant difference in MWT and TWL between group B before treatment and group C (P> 0.05). The histological observation of the sciatic nerve in the 3 groups shows that the epineurium and the perineurium are intact, and the axonal arrangement is generally neat. There is no obvious demyelination and few inflammatory cell infiltration. The sciatic nerve histological score of each group is 1 , The difference was not statistically significant (P> 0.05). Conclusion Repeated (chronic) injection of 0.5% amitriptyline into the sciatic nerve has peripheral anti-hyperalgesia effect on rats with neuropathic pain. The effect of cumulative dose of amitriptyline on rats with neuropathic pain is additive. No obvious pathological changes of the sciatic nerve occur.