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TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model

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Abstract

Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans; however, the underlying mechanisms remain largely unknown. In this study, we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and the voltage-gated K+ channel Kv7.2 (encoded by Kcnq2) to orofacial inflammatory pain in mice. We found that complete Freund’s adjuvant (CFA) injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion (TG) and induced orofacial inflammatory pain. The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression. Moreover, TET1 knockdown in Tet1flox/flox mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors. Conversely, TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia. Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.

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Acknowledgments

We would like to thank Dr. Guoliang Xu (Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, China) for the gift of the Tet1flox/flox mice. This work was supported by the National Natural Science Foundation of China (81771195 and 81971061), and the Program for Innovative Research Team in Universities of Henan Province (22IRTSTHN028).

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  1. Dengcheng Zhan and Jingjing Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Dengcheng Zhan, Jingjing Zhang, Songxue Su, Xiuhua Ren, Sen Zhao, Weidong Zang & Jing Cao

  2. Neuroscience Research Institute, Zhengzhou University, Zhengzhou, 450001, China

    Dengcheng Zhan, Jingjing Zhang, Sen Zhao, Weidong Zang & Jing Cao

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  1. Dengcheng Zhan
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Zhan, D., Zhang, J., Su, S. et al. TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model. Neurosci. Bull. (2023). https://doi.org/10.1007/s12264-023-01139-1

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