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目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对L5脊神经结扎(spinal nerve ligation,SNL)诱导的神经病理性痛(neuropathic pain,NP)大鼠脊髓背角内NMDA受体亚单位NR2B的表达和星形胶质细胞激活的影响。方法:成年雄性SD大鼠48只,随机分为4组:正常组(不做任何处理);SCS组(植入SCS装置并给予SCS刺激);SNL+sham SCS组(给予SNL手术并植入SCS装置,但不进行刺激);SNL+SCS组(SNL手术并给予SCS刺激)。SCS刺激是在SNL术后第6～10 d进行(8 h/d),第10 d刺激结束后处死动物。运用行为学方法检测慢性痛状态下大鼠后肢对机械性刺激的反应阈值;采用免疫组织化学染色和Western blot方法分别检测脊髓背角内NR2B和星形胶质细胞的标志物GFAP的表达变化。结果:(1)SNL术后大鼠手术侧后足机械性痛敏显著增加,第6～10 d给予SCS刺激后,可观察到大鼠的痛行为学表现有明显缓解;(2)免疫组化结果显示:与SNL+sham SCS组相比,SNL+SCS组大鼠脊髓背角内NR2B和GFAP免疫阳性细胞的数量显著减少;(3)Western blot结果显示:给予SCS刺激后,SNL大鼠腰膨大段脊髓背角内NR2B的表达量显著下调,同时GFAP的表达量也明显有所降低。结论:给予SCS刺激可以有效地缓解SNL模型大鼠的神经病理性痛的行为学表现;该作用可能与SCS刺激抑制脊髓背角内NR2B的表达和星形胶质细胞的激活密切相关。
Objective: To investigate the effect of spinal cord stimulation (SCS) on the expression of NMDA receptor subunit NR2B in spinal dorsal horn induced by L5 spinal nerve ligation (SNL) in rats with neuropathic pain (NP) and Effect of Astrocyte Activation. Methods: Forty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups: normal group (without any treatment), SCS group (SCS implanted with SCS stimulation), SNL + sham SCS group SCS device without stimulation); SNL + SCS group (SNL surgery with SCS stimulation). SCS stimulation was performed on day 6 to 10 after SNL (8 h / d), and animals were sacrificed on the 10th day after stimulation. The behavioral methods were used to detect the response threshold of rat hindlimb to mechanical stimulation in chronic pain state. The expression of NR2B and astrocyte marker GFAP in spinal dorsal horn was detected by immunohistochemical staining and Western blot. Results: (1) Mechanical hyperalgesia was significantly increased in the posterior hind limbs of rats after SNL operation. The pain behavior behavior of the rats was significantly relieved after SCS stimulation on the 6th to 10th day. (2) The results showed that compared with SNL + sham SCS group, the number of NR2B and GFAP immunoreactive cells in spinal dorsal horn of SNL + SCS group was significantly decreased compared with SNL + SCS group; (3) Western blot results showed that after SCS stimulation, SNL rats The expression of NR2B in the lumbar spinal dorsal horn was significantly down-regulated while the expression of GFAP was also significantly decreased. CONCLUSIONS: The administration of SCS can effectively relieve the neuropathic pain in SNL model rats. This effect may be related to the inhibition of NR2B expression and activation of astrocytes by SCS in spinal dorsal horn.