| 摘要: |
| 目的 探讨重复经颅磁刺激（rTMS）对慢性背根神经节受压（CCD）致神经病理性疼痛（NPP）大鼠模型的镇痛作用及机制。方法 将36只10周龄雄性SD大鼠随机分为3组：假手术+假刺激组、NPP+假刺激组、NPP+rTMS组，每组成功纳入12只。假手术+假刺激组和NPP+假刺激组大鼠上午、下午均接受假刺激，NPP+rTMS组大鼠上午接受假刺激，下午接受高频rTMS（大脑皮质M1区，20 Hz）。在CCD致NPP模型建立后第8天开始对大鼠进行rTMS真刺激或假刺激干预，连续11 d。rTMS干预前后用von Frey纤维丝和条件性位置偏爱实验分别测定机械痛阈和自发痛。在造模后第20天取大鼠左侧L4～L5节段背根神经节（DRG）及脊髓背角和血清标本，用蛋白质印迹法检测DRG和脊髓背角中卫星胶质细胞和星形胶质细胞活化标志物胶质纤维酸性蛋白（GFAP）及脊髓背角中突触后致密区95（PSD-95）蛋白的表达，ELISA检测血清中促炎因子IL-18和TNF-α水平。结果 与假手术+假刺激组相比，NPP+假刺激组大鼠机械痛阈降低，DRG中GFAP表达增加，脊髓背角中GFAP和PSD-95蛋白表达均增加，血清中IL-18、TNF-α水平均增高，差异均有统计学意义（P均<0.05）；两组大鼠对A、B箱均无偏爱。而NPP+rTMS组（即高频rTMS干预后）大鼠上述改变与NPP+假刺激组相比均被逆转，且大鼠对B箱产生明显偏爱（P均<0.05）。结论 高频rTMS可能通过抑制DRG中卫星胶质细胞活化、抑制脊髓背角中星形胶质细胞活化和突触连接形成及改善炎症微环境，缓解CCD导致的大鼠NPP。 |
| 关键词: 重复经颅磁刺激 神经病理性疼痛 背根神经节 脊髓背角 星形胶质细胞 突触后致密区95 炎症因子 |
| DOI：10.16781/j.0258-879x.2021.07.0749 |
| 投稿时间：2020-02-22修订日期：2020-07-27 |
| 基金项目:国家自然科学基金（81772453，81974358）. |
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| Analgesic effect of repetitive transcranial magnetic stimulation on rats with neuropathic pain caused by chronic compression of dorsal root ganglion and its mechanism |
| ZHANG Ye1,ZHAO Dan1,XU Dong-sheng1,2* |
(1. Rehabilitation Center, Tongji Hospital, Tongji University, Shanghai 200065, China;
2. Department of Orthopaedics, Tongji Hospital, Tongji University, Shanghai 200065, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on rats with neuropathic pain (NPP) caused by chronic compression of dorsal root ganglion (CCD) and to explore the mechanism. Methods A total of 36 male rats aged 10 weeks were evenly randomized into 3 groups:sham operation+sham stimulation group, NPP+sham stimulation group, and NPP+rTMS group. The rats in the sham operation+sham stimulation group and NPP+sham stimulation group received sham stimulation in the morning and afternoon, while the rats in the NPP+rTMS group received sham stimulation in the morning and high frequency rTMS (M1 area of cerebral cortex, 20 Hz) in the afternoon. On the 8th day after CCD-caused NPP modeling, rats were intervened by rTMS or sham stimulation for 11 consecutive days. Von Frey filaments and conditioned place preference test were used to evaluate the mechanical withdrawal threshold and spontaneous pain before and after rTMS intervention. The left L4-L5 dorsal root ganglion (DRG), spinal cord dorsal horn and sera were collected on the 20th day after NPP modeling, the expression levels of glial fibrillary acidic protein (GFAP), an activation marker of satellite glial cells and astrocytes, in DRG and spinal cord dorsal horn and the postsynaptic density-95 (PSD-95) in spinal cord dorsal horn were measured by Western blotting. The interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α) in sera were detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the sham operation+sham stimulation group, the mechanical withdrawal threshold was significantly decreased, the expression of GFAP in DRG was significantly increased, the expression levels of GFAP and PSD-95 in spinal cord dorsal horn were significantly higher, and the serum levels of IL-18 and TNF-α were significantly increased in the NPP+sham stimulation group (all P<0.05); and the rats in the 2 groups had no preference for cage A or cage B. However, these changes were all reversed in the NPP+rTMS group after receiving high-frequency rTMS, and the rats had a preference for cage B compared with the NPP+sham stimulation group (all P<0.05). Conclusion High-frequency rTMS may relieve CCD-caused NPP by inhibiting the activation of satellite glial cells in DRG, by inhibiting astrocyte activation and synaptic connection formation in spinal cord dorsal horn, and by improving inflammatory microenvironment. |
| Key words: repetitive transcranial magnetic stimulation neuropathic pain dorsal root ganglion spinal cord dorsal horn astrocytes postsynaptic density-95 inflammatory factors |
