title: Ca(2+) influx mediates the TRPV4-NO pathway in neuropathic hyperalgesia following chronic compression of the dorsal root ganglion.
abstract: 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 Ca(2+) 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-κB 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-κB activity and NO content in DRG of CCD rats. Moreover, pre-treatment with 4α-PDD attenuated the suppressive effects of mibefradil on CCD-induced neuropathic hyperalgesia, NF-κB activity, and NO production. The data showed that TRPV4-mediated Ca(2+) influx might be engaged in the TRPV4-NO pathway in neuropathic hyperalgesia in the CCD model.
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012, China. Electronic address: wangjie276694704@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Yin
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China. Electronic address: drg98@hotmail.com.
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Yue
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002908:Chronic Disease; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009408:Nerve Compression Syndromes / Q000150:complications / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D017208:Rats, Wistar; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C517592:4alpha-phorbol 12,13-didecanone; D002121:Calcium Channel Blockers; D016328:NF-kappa B; D010704:Phorbols; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D020748:Mibefradil; D009569:Nitric Oxide; D002118:Calcium
keywords: Calcium signalling; Neuropathic hyperalgesia; Nitric oxide; Nuclear factor-kappa B; TRPV4