标题：Ca2+ influx mediates the TRPV4-NO pathway in neuropathic hyperalgesia following chronic compression of the dorsal root ganglion
作者：Wang, Jie; Wang, Xiao-Wei; Zhang, Yang; Yin, Cui-Ping; Yue, Shou-Wei
作者机构：[Wang, Jie; Zhang, Yang; Yin, Cui-Ping; Yue, Shou-Wei] Shandong Univ, Qilu Hosp, Dept Phys Med & Rehabil, Sch Med, Jinan 250012, Peoples R China.; [ 更多
通讯作者地址：[Yue, SW]Shandong Univ, Qilu Hosp, Dept Phys Med & Rehabil, Sch Med, Jinan 250012, Peoples R China.
关键词：Nuclear factor-kappa B; Nitric oxide; TRPV4; Neuropathic hyperalgesia;; Calcium signalling
摘要：Chronic compression of the dorsal root ganglion (DRG) (CCD) in rats is a typical model of neuropathic pain. TRPV4 contributed to mechanical allodynia induced by the CCD model. Our previous study demonstrated that TRPV4 enhances neuropathic hyperalgesia through a NO-cGMP-PKG cascade. However, the underlying mechanism(s) is still largely unknown. Therefore, the aim of the present study was to test whether TRPV4-mediated Ca2+ influx is involved in the TRPV4-NO pathway. Regulation of intracellular calcium concentration by intrathecal injection of TRPV4-targeted siRNA significantly decreased the behavioural hyperalgesia, NF-kappa B activity, and NO content in CCD rats. Intraperitoneal (i.p.) injection of mibefradil significantly induced dose-dependent increases in the paw withdrawal latency (PWL) and mechanical withdrawal thresholds (MWT), as well as decreases in NF-KB activity and NO content in DRG of CCD rats. Moreover, pre-treatment with 4 alpha-PDD attenuated the suppressive effects of mibefradil on CCD-induced neuropathic hyperalgesia, NF-KB activity, and NO production. The data showed that TRPV4-mediated Ca2+ influx might be engaged in the TRPV4-NO pathway in neuropathic hyperalgesia in the CCD model. (C) 2015 Elsevier Ireland Ltd. All rights reserved.