鞘内注射舒芬太尼对神经病理性痛大鼠脊髓背角NMDA受体及CGRP表达的影响

目的 评价鞘内注射舒芬太尼对神经病理性痛大鼠脊髓背角N-甲基-D-天冬氨酸(NMDA)受体及降钙素相关基因肽(CGRP)表达的影响.方法 雄性SD大鼠36只,体重220～280 g,随机分为4组(n=9):正常对照组(C组)、假手术组(S组)、坐骨神经分支选择性损伤组(SNI组)和舒芬太尼+坐骨神经分支选择性损伤组(S+SNI组).SNI组和S+SNI组制备SNI模型,S+SNI组在SNI术后14 d内每天鞘内注射舒芬太尼1 μg(用生理盐水稀释至10 μl),其余各组给予等容量生理盐水.于SNI给药前2 d(基础状态)及给药1、2、7、14 d测定机械痛阈和热缩足潜伏期,分别于给药2、7、14 d测定痛阈后立即处死3只大鼠,采用免疫组化法测定L5节段脊髓背角NMDA受体和CGRP表达水平.结果 与C组和S组比较,SNI组机械痛阚降低,NMDA受体和CGRP表达上调(P<0.01),热缩足潜伏期差异无统计学意义(P>0.05).与SNI组比较,S+SNI组机械痛阈升高,热缩足潜伏期延长,NMDA受体和CGRP表达下调(P<0.01).结论 鞘内注射舒芬太尼可抑制脊髓背角NMDA受体和CGRP表达上调,从而减轻大鼠神经病理性痛.

Effect of intrathecal sufentanil on NMDAR and CGRP expression in dorsal horn of spinal cord in a rat model of neuropathic pain

Objective To evaluate the effect of intrathecai (IT) sufentanil on NMDAR and CGRP expression in dorsal horn of the spinal cord in a rat model of neuropathic pain. Methods Thirty-six healthy male SD rats weighing 220-280 g were randomly divided into 4 groups (n=9 each): group Ⅰ normal control (group C);group Ⅱ sham operation (group S);group Ⅲ spared sciatic nerve injury (group SNI) and group Ⅳ sufentanil + SNI (group S + SNI). A polyethylene micrespinal catheter was inserted through atlanto-occipital membrane into the subarachnoid space and advanced caudally until the tip reached lumbar segment according to Yaksh. In group Ⅲ and Ⅳ left sciatic nerve and its three terminal branches--tibial, common peroneal and sural nerves were exposed. Tibial and common pereneal nerves were ligated and severed at a point distal to the ligature, while sural nerve was kept intact. In group Ⅱ the sciatic nerves and its branches were exposed but not ligated and severed. In group Ⅳ sufentanil 1 μg in normal saline (NS) 10 μl was injected IT once a day for 14 consecutive days after operation. In group Ⅰ , Ⅱ and Ⅲ NS 10 μl was injected IT instead of sufentanil. Paw withdrawal threshold to von Frey filament stimulation and paw withdrawal latency to noxious thermal stimuli were measured 2 day before (baseline) and 1,2,7, 14 d of IT sufentanil/NS injection. Three animals were killed at 2, 7 and 14 d of IT injection respectively. The lumbar segment of the spinal cord was removed for determination of NMDAR and CGRP expression in the dorsal horn of the spinal cord (L5) using immuno-histochemistry. Results Compared with group C and S (Ⅰ, Ⅱ), mechanical pain threshold was significantly decreased and the expression of NMDAR and CGRP was significantly increased in group SNI (Ⅲ), but there was no significant difference in thermal paw withdrawal latency. Compared with group SNI (Ⅲ), mechanical pain threshold was increased and thermal paw withdrawal latency was prolonged in group S + SNI (Ⅳ) and the expression of NMDAR and CGRP was decreased. Conclusion Intrathecal sufentanil can reduce neuropathic pain by inhibiting the up-regulation of NMDAR and CGRP expression in the dorsal horn of the spinal cord.