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CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice

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Abstract

Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3−/− mice, CXCL10 did not increase the number of APs, and the SNL-induced increase of the numbers of APs in DRG neurons was reduced. Finally, CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons. Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10. Our data indicate that CXCR3, activated by CXCL10, mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability, which contributes to the maintenance of neuropathic pain.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31871064 and 32030048), the Natural Science Research Program of Jiangsu Province, China (BK20171255), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province, China (KYCX19 2088).

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  1. Yan-Fang Kong and Wei-Lin Sha have contributed equally to this work.

Authors and Affiliations

  1. Institute of Pain Medicine, Institute of Nautical Medicine, Nantong University, Nantong, 226019, China

    Yan-Fang Kong, Wei-Lin Sha, Xiao-Bo Wu, Lin-Xia Zhao, Ling-Jie Ma & Yong-Jing Gao

  2. Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China

    Yong-Jing Gao

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  1. Yan-Fang Kong
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Kong, YF., Sha, WL., Wu, XB. et al. CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice. Neurosci. Bull. 37, 339–352 (2021). https://doi.org/10.1007/s12264-020-00608-1

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  • DOI: https://doi.org/10.1007/s12264-020-00608-1

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