激活α2A肾上腺素受体抑制背根神经节卫星胶质细胞活性缓解镜像痛敏  

Activation ofα2A adrenergic receptor alleviates mirror-image pain via inhibiting the activation of dorsal root ganglia satellite glia

作　　者：杨盼 闫成祥 朱利香 姜鸣 杨亮[1,2,3] 侯仁浩 王江博[1] 曹园园[1] 刘霞 白占涛[1,2,3] YANG Pan;YAN Chengxiang;ZHU Lixiang;JIANG Ming;YANG Liang;HOU Renhao;WANG Jiangbo;CAO Yuanyuan;LIU Xia;BAI Zhantao(School of Life Science&Research Center for Natural Peptide Drugs,Shaanxi Engineering&Technological Research Center for Conservation&Utilization of Regional Biological Resources,Yanan University,Yanan 716000,China;Yanan Engineering&Technological Research Center for Resource Peptide Drugs,Yanan 716000,China;Yanan Key Laboratory for Neural Immuno-Tumor and Stem Cell,Yanan 716000,China)

机构地区：[1]延安大学生命科学学院多肽药物研究中心,陕西省区域生物资源保护与利用工程技术研究中心,延安716000 [2]延安多肽药物工程技术研究中心,延安716000 [3]延安神经免疫肿瘤与干细胞重点实验室,延安716000

出　　处：《中国疼痛医学杂志》2023年第8期572-582,共11页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(82101507,31960174,82160230,82260234);陕西省秦创原“科学家+工程师”队伍建设项目(2022KXJ-152);陕西省教育厅服务地方专项计划项目(22JC060);延安大学科研项目(CXY202003,CXY202004,YDBK 2019-41);大学生创新创业训练计划(D2022026)。

摘　　要：目的:躯体单侧组织损伤引发对侧疼痛反应,称为镜像痛敏。镜像痛敏的病理机制尚不明确,缺乏特异性靶标,影响其治疗。本研究拟阐释背根神经节中α2A肾上腺素受体和神经胶质细胞介导镜像痛敏的发生机制。方法:采用行为药理学、实时荧光定量PCR、免疫荧光和免疫印迹等技术研究背根神经节中α2A肾上腺素受体和神经胶质细胞介导镜像痛敏的机制。结果:背根神经节中α2A肾上腺素受体参与了镜像痛敏的发生发展。激活α2A肾上腺素受体显著缓解镜像痛敏行为。疼痛刺激下,双侧背根神经节中胶质细胞被差异激活,而激活α2A肾上腺素受体进一步活化背根神经节神经胶质细胞。此外,激活α2A肾上腺素受体显著降低卫星胶质细胞中α2A肾上腺素受体的表达,而不影响小胶质细胞中α2A肾上腺素受体的表达。结论:背根神经节卫星胶质细胞中的α2A肾上腺素受体是镜像痛敏的重要分子传感器,激活α2A肾上腺素受体改善镜像痛敏行为。Objective:Unilateral injury often causes contralateral pain response,which is called mirror-image pain(MIP).The pathological mechanism of MIP is not clear yet,and there is no specific target,which severely limit its treatment.This study aims to elucidate the mechanism of MIP mediated byα2A adrenergic receptors(α(2A)AR)and glial cells in the dorsal root ganglia(DRG).Methods:Behavioral pharmacology,real-time fluorescence quantitative PCR,immunofluorescence,and immunoblotting techniques were used to study the role ofα(2A)AR and glial cells in DRG under MIP.Results:In the DRGα(2A)AR is involved in the occurrence and development of mirror pain sensitivity.Activation ofα(2A)AR significantly alleviates mirror pain sensitivity behaviors.Under pain stimulation,glial cells in bilateral DRG are differentially activated,activation ofα(2A)AR significantly activate glial cells in the dorsal root ganglia.In addition,activation ofα(2A)AR significantly reduces the expression ofα(2A)AR in satellite glial cells,but without affecting the expression ofα(2A)AR in microglia.Conclusion:In the satellite glial cells of the DRG,α(2A)AR is an important molecular sensor for MIP,and activation ofα(2A)AR can improve MIP behaviors.

关 键 词：背根神经节 α2A肾上腺素受体 卫星胶质细胞 镜像痛敏 

分 类 号：R402[医药卫生—临床医学]