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触液核GluN2B-BDNF通路介导大鼠神经病理性疼痛的发生

王溢文¹, 张尧尧¹, 吴征元¹, 程二登², 陈燕琪¹, 申文¹, 张励才¹, 张苏明^1,3,*

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

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。

关键词： 触液核; GluN2B; CB-HRP; BDNF; 神经病理性疼痛

分类号：R338

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

WANG Yi-Wen¹, ZHANG Yao-Yao¹, WU Zheng-Yuan¹, CHENG Er-Deng², CHEN Yan-Qi¹, SHEN Wen¹, ZHANG Li-Cai¹, ZHANG Su-Ming^1,3,*

¹Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, China；²Department of Anesthesiology, Shanghai Minhang Central Hospital, Shanghai 201100, China；³Department of Intensive Care Unit, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221009, China

Abstract

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 (CB-HRP) 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.

Key words: cerebrospinal fluid-contacting nucleus; GluN2B; CB-HRP; BDNF; neuropathic pain

收稿日期：2020-06-14　　录用日期：2020-09-21

通讯作者：张苏明　　E-mail: samuel3766@126.com

DOI: 10.13294/j.aps.2020.0094

引用本文：

王溢文, 张尧尧, 吴征元, 程二登, 陈燕琪, 申文, 张励才, 张苏明. 触液核GluN2B-BDNF通路介导大鼠神经病理性疼痛的发生[J]. 生理学报 2021; 73 (2): 223-232.

WANG Yi-Wen, ZHANG Yao-Yao, WU Zheng-Yuan, CHENG Er-Deng, CHEN Yan-Qi, SHEN Wen, ZHANG Li-Cai, ZHANG Su-Ming. GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats. Acta Physiol Sin 2021; 73 (2): 223-232