触液核GluN2B-BDNF通路介导大鼠神经病理性疼痛的发生  

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats

作　　者：王溢文 张尧尧 吴征元 程二登 陈燕琪 申文 张励才 张苏明 WANG Yi-Wen;ZHANG Yao-Yao;WU Zheng-Yuan;CHENG Er-Deng;CHEN Yan-Qi;SHEN Wen;ZHANG Li-Cai;ZHANG Su-Ming(Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China;Department of Anesthesiology,Shanghai Minhang Central Hospital,Shanghai 201100,China;Department of Intensive Care Unit,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221009,China)

机构地区：[1]徐州医科大学麻醉学重点实验室,徐州221004 [2]上海市闵行区中心医院麻醉科,上海201100 [3]徐州医科大学附属医院东院重症医学科,徐州221009

出　　处：《生理学报》2021年第2期223-232,共10页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.81571066);the Natural Science Foundation of Jiangsu Province,China(No.BE2015626)。

摘　　要：本研究旨在探讨触液核GluN2B-BDNF通路在神经病理性疼痛中的作用。应用侧脑室注射特异性触液核示踪剂霍乱毒素亚单位B与辣根过氧化物酶复合物(cholera toxin subunit B conjugated with horseradish peroxidase,CB-HRP)的方法标记触液核;通过免疫荧光双标染色和Western blot观察大鼠触液核GluN2B和BDNF的表达;采用坐骨神经慢性压迫性损伤法(chronic constriction injury of sciatic nerve,CCI)建立大鼠慢性神经病理性疼痛模型;通过侧脑室注射GluN2B拮抗剂和BDNF中和抗体观察CCI大鼠的行为学变化。结果显示,GluN2B和BDNF均在触液核内表达,并且在CCI大鼠表达上调;侧脑室注射GluN2B拮抗剂或BDNF中和抗体能够减轻CCI大鼠的热痛觉过敏和机械性痛觉超敏;而且侧脑室注射GluN2B拮抗剂能够逆转CCI大鼠BDNF的表达上调。以上结果提示,大鼠触液核内有GluN2B和BDNF的表达,并且触液核GluN2B-BDNF通路参与了大鼠神经病理性疼痛的发生。The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus(CSF-CN)in neuropathic pain.Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase(CBHRP)was used to label the CSF-CN.Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN.Chronic constriction injury of sciatic nerve(CCI)rat model was used to duplicate the neuropathic pain.Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats.GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats.Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats.Moreover,the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981.These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.

关 键 词：触液核 GluN2B CB-HRP BDNF 神经病理性疼痛 

分 类 号：R338[医药卫生—人体生理学]