普瑞巴林对坐骨神经损伤大鼠疼痛行为及背根神经节p-JNK表达的影响

Effect of Pregabalin on p-JNK Expression and Pain Behavior in Rat Model of Chronic Ischiadic Injury

目的观察普瑞巴林对坐骨神经损伤所致的神经病理性疼痛行为和背根神经节p-Jun氨基末端激酶(p-JNK)表达的影响。方法选择30只清洁级雌性SD大鼠,采用随机数字表法分为假手术组、坐骨神经损伤组和普瑞巴林组,每组10只。假手术组仅分离大鼠坐骨神经而不结扎,坐骨神经损伤组和普瑞巴林组结扎坐骨神经,普瑞巴林组大鼠于术后第1日开始胃内灌注普瑞巴林10 mg/kg,假手术组和坐骨神经损伤组给予等量的生理盐水。于术前、术后第7、14日测定各组大鼠的热痛阈,于术后第7、14日测定背根神经节p-JNK的表达情况。结果三组大鼠的热痛阈组间比较、不同时间点比较以及组间·不同时间的比较差异均有统计学意义(P<0.05),其中假手术组不同时间点比较波动不大,而坐骨神经损伤组与普瑞巴林组逐渐降低,且坐骨神经损伤组大鼠的热痛阈低于普瑞巴林组。假手术组、坐骨神经损伤组和普瑞巴林组大鼠术后第7日和14日p-JNK的免疫组织化学评分比较差异有统计学意义[(5.00±1.15)比(9.45±1.89)比(5.25±1.13)]、[(5.25±2.22)比(8.10±1.50)比(6.15±0.91)](P<0.05),其中术后第7日和14日,坐骨神经损伤组大鼠的p-JNK较假手术组和普瑞巴林组高,比较差异有统计学意义(P<0.05),术后第7日,假手术组与普瑞巴林组比较差异无统计学意义(P>0.05),术后第14日,假手术组与普瑞巴林组比较差异无统计学意义(P>0.05)。术后第14日三组大鼠的p-JNK免疫组织化学评分与术后第7日比较,假手术组无显著变化(P>0.05),坐骨神经损伤组与普瑞巴林组显著降低(P<0.05)。结论普瑞巴林对坐骨神经损伤所致的神经病理性疼痛有明显的镇痛作用,其机制可能与抑制背根神经节pJNK的活化有关。

Objective To observe the effect of pregabalin on expression of p-JNK in dorsal mot ganglia and pain behavior induced by chronic sciatic nerve injury in rat model. Methods Total of 30 female SD rats were divided into 3 groups according to random number table method,including sham-operation group, sciatic nerve injury group and pregabalin group ,10 rats each. In sham-operation group,the sciatic nerve was exposed but not ligated, in sciatic nerve injury group and pregabalin group, the sciatic nerve was exposed and ligated by sutures. Pregabalin 10 mg/kg i. g. was administered in pregabalin group from the first day after operation, and same volume of physiological saline was given to sham-operation and sciatic nerve injury groups. Thermal pain threshold was measured by paw withdrawal latencies（PWL） before operation and postoperative 7 and 14 days, p-JNK expression was detected by immunohistochemical technique postoperative 7 and 14 days. Results PWT value of the three groups at different groups, different points and different groups·points were significantly different（ P 〈 0.05 ）, the PWT value of sham-operation group was stable, and the other two groups were decreased, and the PWT value of sciatic nerve injury group was higher than pregabalin group. The p-JNK of sham-operation group, sciatic nerve injury group and pregabalin group at 7th day and 14th day were [ （5.00±1.15） vs （9.45±1.89） vs （5.25±1.13） ] ,[ （5.25±2.22） vs （8, 10±1.50） vs （6. 15±0. 91 ） ] （P 〈 0.05 ）, the p-JNK of sciatic nerve injury group at 7th day and 14th day were higher than sham-operation group and pregabalin group with statistically significant difference （P 〈 0.05 ） ;there was no significant difference between sham-operation group and pregabalin group at 7th day after operation （ P 〉 0.05 ）, while there was significant difference at 14th day after operation（ P 〈 0.05 ）. The p-JNK level of sham-operation group at 14th day had no significant change （P 〉 0.05 ） , but sciatic nerve injury group and pregabalin group were significantly lower （ P 〈 0.05 ）. Conclusion Pregabalin shows an analgesic effect on neuropathic pain caused by sciatic nerve injury, and its mechanism is possibly associated with the inhibition of p-JNK activation.