Chemokine CXCL10/CXCR3 signaling contributes to neuropathic pain in spinal cord and dorsal root ganglia after chronic constriction injury in rats
Chemokine CXCL10/CXCR3 signaling contributes to neuropathic pain in spinal cord and dorsal root ganglia after chronic constriction injury in rats
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DOI：
10.1016/j.neulet.2018.11.021
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发表时间：
2019-02-16
影响因子：
2.5
通讯作者：
Xu, Zhongling
中科院分区：
文献类型：
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作者：
Chen, Yonglin;Yin, Dekun;Xu, Zhongling
炎症因子和趋化因子在神经性疼痛（NP）的发生和持续中起重要作用。慢性收缩损伤（CCI）增强了p-ERK的激活，其参与神经性疼痛。虽然趋化因子CXCL10及其受体CXCR3与瘙痒的病理生理有关，但其在神经性疼痛中的作用尚未得到充分研究。在这项研究中，我们使用一个完善的CCI模型确定了CXCL10-CXCR3轴在NP中的作用。CCI显著诱导机械异常性痛和热痛觉过敏。疼痛过程结束后，大鼠背根神经节（DRG）神经元和脊髓（SC）神经元中CXCL10和CXCR3表达均显著升高。此外，发现鞘内注射CXCR3抑制剂AMG487以剂量依赖的方式减轻CCI患者的疼痛超敏反应。在鞘内注射AMG487后，PERK的表达也被抑制，并伴有痛觉过敏的明显缓解，这表明CXCL10/CXCR3的相互作用可能通过调节SC中的p-ERK信号参与神经性疼痛。总之，这些发现表明CXCL10/CXCR3信号通路在CCI中至关重要。
Inflammatory cytokines and chemokines play essential roles in the occurrence and persistence of neuropathic pain (NP). Chronic constriction injury (CCI) enhances the activation of p-ERK, which is involved in neuropathic pain. Although the chemokine CXCL10 and its receptor CXCR3 are implicated in the pathophysiology of itch, it is largely unexplored for neuropathic pain. In this study, we determined the role of the CXCL10-CXCR3 axis in NP using a well-established CCI model. CCI significantly induced mechanical allodynia and thermal hyperalgesia. Following the pain course, a significant increase of CXCL10 and CXCR3 in both dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons was detected in rats. Furthermore, intrathecal injection of CXCR3 inhibitor AMG487 was found to attenuate pain hypersensitivity in a dose-dependent manner in CCI. The expression of PERK was also depressed after intrathecal injection of AMG487 associated with a significant laxation of hyperalgesia, which demonstrated that the interaction of CXCL10/CXCR3 possibly took part in neuropathic pain by regulating p-ERK signaling in the SC. Overall, these findings demonstrate that the CXCL10/CXCR3 signaling pathway is critical in CCI.