JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury

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• 作者：Yan Chen ; Xiangdong Chen ; Jiang Yu ; Xingguo Xu ; Xiaojia Wei…
• 刊名：Neurochemical Research
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：41
• 期：5
• 页码：1119-1129
• 全文大小：5,606 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Biochemistry
  Neurology
  
• 出版者：Springer Netherlands
• ISSN：1573-6903
• 卷排序：41

文摘

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.KeywordsNeuropathic painJun activation domain-binding protein (JAB1)c-Jun N-terminal kinase (JNK)Nuclear factor-kappa B (NF-κB)Chronic constriction injury (CCI)