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Chemokine CXCL13 activates p38 MAPK in the trigeminal ganglion after infraorbital nerve injury

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Abstract

Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the trigeminal ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified. Here, we show that the unilateral partial infraorbital nerve ligation (pIONL) induced a profound orofacial pain in wild-type (WT) mice. Western blot results showed that pIONL induced p38 but not JNK activation in the TG of WT mice. However, the orofacial pain induced by pIONL was alleviated in Cxcr5 −/− mice, and the activation of p38 was also abrogated in Cxcr5 −/− mice. Furthermore, intra-TG injection of CXCL13 evoked mechanical hypersensitivity and increased p-p38 expression in WT mice. But CXCL13 had no effect on pain behavior or p-p38 expression in Cxcr5 −/− mice. Finally, pretreatment with p38 inhibitor, SB203580, attenuated the pIONL-induced mechanical allodynia and decreased the mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the TG. Taken together, our data suggest that CXCL13 acts on CXCR5 to increase p38 activation and further contributes to the pathogenesis of orofacial neuropathic pain.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (NSFC 31371121 and 81300954), the Natural Science Research Program of Jiangsu Province (13KJB180017), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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    Authors and Affiliations

    1. Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Inflammation and Molecular Drug Target, Nantong University, 9 Seyuan Road, Nantong, Jiangsu, 226019, China

      Qian Zhang, De-Li Cao, Xue-Qiang Bai, Yong-**g Gao & **ao-Bo Wu

    2. Department of Orthopedics, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China

      Ming-Di Zhu

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    Qian Zhang and Ming-Di Zhu contributed equally to this work.

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    Zhang, Q., Zhu, MD., Cao, DL. et al. Chemokine CXCL13 activates p38 MAPK in the trigeminal ganglion after infraorbital nerve injury. Inflammation 40, 762–769 (2017). https://doi.org/10.1007/s10753-017-0520-x

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