title: JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury.
abstract: Neuropathic pain, caused by a lesion or dysfunction of the somatosensory nervous system, is a severe debilitating condition with which clinical treatment remains challenging. Jun activation domain-binding protein (JAB1) is a multifunctional protein that participates in several signaling pathways, controlling cell proliferation and apoptosis. However, the expression and possible function of JAB1 in the pathogenesis of neuropathic pain has not been elucidated. This study aimed to investigate the possible involvement of JAB1. Here, employing a neuropathic pain model induced by chronic constriction injury (CCI) on rats, we reported the role of JAB1 in the maintenance of neuropathic pain. By western blot, we found that CCI markedly up-regulated JAB1 expression in the dorsal root ganglion (DRG) and spinal cord. Immunofluorescent assay demonstrated that JAB1 was extensively localized in IB4-, CGRP- and NF200-positive neurons in the injured L5 DRG, and mainly co-localized with NeuN in spinal cord. In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathecal injection of JAB1 siRNA significantly attenuated the CCI-induced JNK and p65 phosphorylation and alleviated both mechanical allodynia and heat hyperalgesia in rats. Taken together, these results suggested that JAB1 promotes neuropathic pain via positively regulating JNK and NF-κB activation.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gu
authors.affiliation: Laboratory Animal Center, Nantong University, Nantong, 226001, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. zdm@ntu.edu.cn.|Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China. zdm@ntu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China. Xu_zhongling@sina.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China. Xu_zhongling@sina.com.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D000075686:COP9 Signalosome Complex; D003251:Constriction, Pathologic / Q000150:complications; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D011506:Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism; D014110:Touch
chemical_list: C490121:Gps1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D000075686:COP9 Signalosome Complex
keywords: Chronic constriction injury (CCI); Jun activation domain-binding protein (JAB1); Neuropathic pain; Nuclear factor-kappa B (NF-κB); c-Jun N-terminal kinase (JNK)