title: Urotensin II inhibitor eases neuropathic pain by suppressing the JNK/NF-κB pathway.
abstract: Urotensin II (U-II), a cyclic peptide originally isolated from the caudal neurosecretory system of fishes, can produce proinflammatory effects through its specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating disease, is related to excessive inflammation in the spinal dorsal horn. However, the relationship between U-II and neuropathic pain has not been reported. This study was designed to investigate the effect of U-II antagonist on neuropathic pain and to understand the associated mechanisms. We reported that U-II and its receptor GPR14 were persistently upregulated and activated in the dorsal horn of L4-6 spinal cord segments after chronic constriction injury (CCI) in rats. Intrathecal injection of SB657510, a specific antagonist against U-II, reversed CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor-κB (NF-κB) p65 as well as subsequent secretion of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). It was also showed that both the JNK inhibitor SP600125 and the NF-κB inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical allodynia in CCI rats. Our present research showed that U-II receptor antagonist alleviated neuropathic pain possibly through the suppression of the JNK/NF-κB pathway in CCI rats, which will contribute to the better understanding of function of U-II and pathogenesis of neuropathic pain.
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Zhao
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Hao
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China.
authors.forename: Yang-Zi
authors.initials: YZ
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China 375630616@qq.com chzhou1212@163.com.|Department of Anesthetic PharmacologyXuzhou Medical University, Xuzhou, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory of AnesthesiologyXuzhou Medical University, Xuzhou, China 375630616@qq.com chzhou1212@163.com.|Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyXuzhou Medical University, Xuzhou, China.
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D014579:Urotensins / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C553589:SB 657510; D013449:Sulfonamides; D014579:Urotensins; C029677:urotensin II
keywords: JNK; NF-κB; Urotensin II antagonists; neuropathic pain