2. Academic Validation
  3. 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

  • Neurosci Lett. 2019 Feb 16;694:20-28. doi: 10.1016/j.neulet.2018.11.021.
Yonglin Chen 1,  Dekun Yin 2,  Bingbing Fan 3,  Xiang Zhu 1,  Qiuping Chen 1,  Yao Li 1,  Shunxing Zhu 4,  Rongxiang Lu 5,  Zhongling Xu 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong 226001, China.
  • 2 Department of Anesthesiology, Funing People's Hospital of Jiangsu, Jiangsu Province, 224400, China.
  • 3 Department of Radiology, Zhongshan Hospital and Shanghai Institute of Medical Imaging, Department of Medical Imaging, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 4 Laboratory Animal Center, Nantong University, Nantong 226001, China.
  • 5 Department of Anesthesiology, Taizhou People's Hospital, Taizhou, Jiangsu Province, 225300, China. Electronic address: [email protected].
  • 6 Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: [email protected].
PMID: 30448292 DOI: 10.1016/j.neulet.2018.11.021
Abstract

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 p-ERK 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.

Keywords

CXCL10; CXCR3; Chronic constriction injury (CCI); Neuropathic pain; p-ERK.

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