JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury
JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury
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JAB1 通过调节慢性缩窄性损伤后 JNK 和 NF-kappaB 的激活来参与神经病理性疼痛。
DOI：
10.1007/s11064-015-1802-z
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Xu, Zhongling
中科院分区：
文献类型：
--
作者：
Chen, Yan;Chen, Xiangdong;Xu, Zhongling
由躯体感觉神经系统的病变或功能障碍引起的神经性疼痛是一种严重的使人衰弱的病症，其临床治疗仍然具有挑战性。Jun激活结构域结合蛋白（JAB 1）是一种多功能蛋白，参与多种信号通路，控制细胞增殖和凋亡。然而，JAB 1在神经病理性疼痛的发病机制中的表达和可能的功能尚未阐明。本研究旨在探讨JAB 1可能参与的机制。在这里，采用慢性压迫性损伤（CCI）诱导的大鼠神经病理性疼痛模型，我们报告了JAB 1在神经病理性疼痛的维持中的作用。Western blot结果显示CCI可显著上调JAB 1在背根神经节（DRG）和脊髓的表达。免疫荧光检测显示，JAB 1广泛定位于损伤L5背根节的IB 4、CGRP和NF 200阳性神经元，主要与NeuN共定位于脊髓。此外，我们发现CCI在体内诱导p65和JNK的磷酸化。鞘内注射JAB 1 siRNA可显著减弱CCI诱导的JNK和p65磷酸化，并减轻大鼠的机械异常性疼痛和热痛觉过敏。综上所述，这些结果表明，JAB 1通过正向调节JNK和NF-κ B活化来促进神经病理性疼痛。
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-kappa B activation.