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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

Received: 2020-06-14　　Accepted: 2020-09-21

Corresponding author: 张苏明　　E-mail: samuel3766@126.com

DOI: 10.13294/j.aps.2020.0094

Citing This Article：

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