表没食子儿茶素没食子酸酯缓解高频刺激诱导的雌性小鼠慢性原发性疼痛  

Intrathecal Injection of(-)-Epigallocatechin Gallate(EGCG)Alleviates Chronic Primary Pain Induced by High-frequency Stimulation in Female Mice

作　　者：唐源 金冬梅[2] 揭英桃 林震嘉 熊媖 彭湘格 周利君[1] 谈智[1] TANG Yuan;JIN Dong-mei;JIE Ying-tao;LIN Zhen-jia;XIONG Ying;PENG Xiang-ge;ZHOU Li-jun;TAN Zhi(Department of Physiology,Zhongshan School of Medical,Sun Yat-sen University,and Center for Pain Research,Sun Yat-sen University,Guangzhou 510080,China;Department of Rehabilitation Medicine,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,510120,China)

机构地区：[1]中山大学中山医学院生理教研室//中山大学疼痛研究中心,广东广州510080 [2]中山大学孙逸仙纪念医院康复医学科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2022年第2期221-228,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81771204);广东省自然科学基金(2021A1515011742,2021A1515011201,2020A1515010204,2019A1515011838)。

摘　　要：【目的】初步探究表没食子儿茶素没食子酸酯(EGCG)对高频刺激(HFS)诱导雌性小鼠慢性原发性疼痛的镇痛作用及其机制。【方法】采用10 V的HFS(波宽0.5 ms,100 Hz,4串,每串持续1 s,间隔10 s)左后肢坐骨神经建立雌性小鼠慢性原发性疼痛模型。将小鼠随机分为假手术组、溶剂(生理盐水)+HFS组、不同浓度EGCG+HFS组(每组4~5只)。手术前1 h,鞘内注射10μL溶剂或EGCG(10、20、50、200μmol/L)。采用后爪机械撤足阈值(PWT)和镇痛效率评价EGCG的治疗效果。最后用免疫荧光法检测腰段脊髓蛋白表达,探讨其可能的作用机制。【结果】与溶剂HFS组比较,EGCG鞘内注射剂量依赖性缓解雌性小鼠HFS引起的机械痛敏,其最大镇痛效率达84.95%。EGCG还可阻断疼痛雌性小鼠同侧腰段脊髓背角c-Fos(神经元兴奋性标记物)阳性神经元数量以及降钙素基因相关肽(CGRP+)终末、Iba1(小胶质细胞标记物)、GFAP(星形胶质细胞标记物)表达的增加。【结论】鞘内注射EGCG可通过抑制脊髓背角突触前CGRP终末增加、突触后神经元兴奋性以及胶质细胞激活,对HFS诱导的慢性原发性疼痛产生镇痛作用。【Objective】To investigate the analgesic effect and its mechanism of(-)-gallocatechin gallate(EGCG)on high-frequency stimulation(HFS)-induced chronic primary pain in female mice.【Methods】The model of chronic primary pain in female mice were established by HFS of sciatic nerve in left hind limb at 10 V(100 Hz,0.5 ms,4 trains of 1-s du⁃ration at 10-s intervals).The mice were randomly divided into sham operation group,vehicle(saline)+HFS group,dif⁃ferent concentrations of EGCG+HFS groups(4~5 mice in each group).10μL EGCG(10,20,50,200μmol/L)or vehi⁃cle was injected intrathecally 1 h before surgery.The therapeutic effect of EGCG was evaluated by paw withdrawal thresh⁃old(PWT)and analgesic efficiency.Immunofluorescence of lumbar spinal cord was used to evaluate the possible mecha⁃nisms.【Results】Compared with vehicle HFS group,intrathecal administration of EGCG alleviated HFS-induced mechani⁃cal allodynia in a dose-dependent manner,and the maximum analgesic efficiency was 84.95%.EGCG also blocked the in⁃creases in c-Fos(a marker for neuronal excitability)positive neurons and the expressions of calcitonin gene-related pep⁃tide(CGRP+)terminals,Iba1(a marker for microglia)and GFAP(a marker for astrocytes)in the ipsilateral spinal dorsal horn.【Conclusion】Intrathecal injection of EGCG exerts an analgesic effect against HFS-induced chronic primary pain,mediated by inhibiting the increases in presynaptic CGRP+terminals,postsynaptic neuronal excitability and glial activation in the spinal dorsal horn.

关 键 词：慢性原发性疼痛 表没食子儿茶素没食子酸酯 高频刺激 C-FOS 降钙素基因相关肽 

分 类 号：R758.31[医药卫生—皮肤病学与性病学]