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脊髓电刺激诱导小胶质细胞极化提高痛阈的机制研究

A study on the mechanism of microglia polarization induced by spinal cord stimulation increasing mechanical threshold

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【作者】 董莎娜罗清甜周晓琴李楠张咏芳季涵璞熊东林肖礼祖罗裕辉樊碧发蒋昌宇

【Author】 DONG Sha-na;LUO Qing-tian;ZHOU Xiao-qin;LI Nan;ZHANG Yong-fang;JI Han-pu;XIONG Dong-lin;XIAO Li-zu;LUO Yu-hui;FAN Bi-fa;JIANG Chang-yu;Guangdong Medical University;Department of Gastroenterology, Shenzhen Nanshan People’s Hospital;Department of Anesthesiology, Dongguan Hospital of Guangzhou University of Chinese Medicine;Department of Pain Medicine, Shenzhen Nanshan People’s Hospital;Shenzhen University Health Science;Department of Pain Medicine, China-Japan Friendship Hospital;

【通讯作者】 樊碧发;蒋昌宇;

【机构】 广东医科大学深圳市南山区人民医院消化科东莞市中医院麻醉科深圳市南山区人民医院疼痛科深圳大学医学部中日友好医院疼痛科

【摘要】 目的:探讨脊髓电刺激(spinal cord stimulation, SCS)治疗慢性疼痛的神经免疫机制。方法:在健康小鼠中植入电极,进行连续SCS,观察机械痛阈值的改变和脊髓中小胶质细胞的极化状态。测定脊髓和脑脊液中转化生长因子-β(transforming growth factor-β, TGF-β)的表达水平,以及抑制TGF-β功能后SCS对机械痛阈值改变的影响。结果:电极植入术未改变小鼠的机械痛阈值和运动能力。连续SCS可显著提高小鼠的机械痛阈,增加脊髓背角中小胶质细胞M2极化水平和TGF-β的表达,鞘内注射TGF-β抗体减弱SCS对机械痛阈值的影响。结论:连续的SCS通过激活脊髓小胶质细胞并使其进入M2极化状态,释放TGF-β,进而上调疼痛阈值发挥镇痛作用。

【Abstract】 Objective: To investigate the neuroimmune mechanism of spinal cord stimulation(SCS) in the treatment of chronic pain. Methods: Electrodes were implanted in healthy mice and continuous SCS was performed to observe the changes in mechanical pain threshold and the polarisation status of microglia in the spinal cord. The expression levels of transforming growth factor-β(TGF-β) in the spinal cord and cerebrospinal fuid were measured, and the efects of SCS on the alteration of mechanical pain threshold after inhibiting the function of TGF-β were determined. Results: Electrode implantation did not infuence the mechanical pain threshold and locomotor ability of mice. Continuous SCS signifcantly increased the mechanical pain threshold, the M2 polarisation level and TGF-β expression in microglia in the dorsal horn of the spinal cord, and intrathecal injection of TGF-β antibody attenuated the efect of SCS on the mechanical pain threshold. Conclusion: Continuous SCS exerts analgesic efects by activating spinal microglia into M2 polarised state and releasing TGF-β, and then up-regulates the pain threshold.

【基金】 国家自然科学基金(82171221);广东省基础与应用基础研究基金(2021A1515110799、2023A1515010144);深圳市科技计划资助(JCYJ20220530142000001);深圳市科技创新委员会基础研究面上项目(JCYJ20220818103206013);深圳市科技创新委员会基础研究重点项目(JCYJ20220818103206013);深圳市南山区卫生健康系统科技重大项目(NSZD2024015);深圳市医疗卫生三名工程引进“中日友好医院樊碧发教授疼痛医学团队”项目(SZSM202103018);国家重点研发计划“主动健康和人口老龄化科技应对”重点专项(2022YFC3602201)
  • 【文献出处】 中国疼痛医学杂志 ,Chinese Journal of Pain Medicine , 编辑部邮箱 ,2025年07期
  • 【分类号】R402
  • 【下载频次】34
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