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TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats

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Abstract

Neuropathic pain is elicited after a serious disorder of the nervous system and is along with the neural damage. It is usually chronic and challenging to treat. Transcription factor 4 (TCF4) is a key transcription factor of Wnt signaling system. Recent studies have shown that TCF4 interacts with β-catenin in the Wnt signaling pathway and coactivates downstream target genes in diverse systems. However, it is not well elucidated in the pathogenesis of neuropathic pain. In the present study, we investigated the role of TCF4 in the maintenance of neuropathic pain after chronic constriction injury (CCI) in rats. CCI induced persistent TCF4 upregulation in the dorsal root ganglion and spinal cord. Interestingly, TCF4 was mainly colocalized with neurons in the injured dorsal root ganglion and spinal cord on CCI day 7. Moreover, the expression patterns of β-catenin and glycogen synthase kinase-3β (GSK-3β) were parallel with that of TCF4 in vivo studies. Intrathecal injection of Wnt/β-catenin pathway inhibitor IWR-1-endo and TCF4 small interfering RNA (siRNA) significantly attenuated CCI-induced mechanical allodynia and heat hyperalgesia. The results suggest that TCF4 in the dorsal root ganglion and spinal cord is involved in the maintenance of CCI-induced neuropathic pain. Targeting TCF4 or Wnt/β-catenin signaling may be a potential treatment for chronic neuropathic pain.

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Acknowledgments

This work were supported by National Basic Research Program of China (973 Program, No. 2012CB822104), National Natural Science Foundation of China (31170766), Nantong City Social Development Projects funds (HS2012032), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    Authors and Affiliations

    1. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China

      Zhongling Xu, Yan Chen & Dekun Yin

    2. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China

      Zhongling Xu, Yan Chen, Dekun Yin & Dongmei Zhang

    3. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China

      Jiang Yu & Xiangdong Chen

    4. Laboratory Animal Center, Nantong University, Nantong, 226001, China

      Chun Liu

    5. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China

      Dongmei Zhang

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    1. Zhongling Xu
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    2. Yan Chen
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    3. Jiang Yu
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    Correspondence to Xiangdong Chen or Dongmei Zhang.

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    Zhongling Xu and Yan Chen contributed equally to this work.

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    Xu, Z., Chen, Y., Yu, J. et al. TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats. J Mol Neurosci 56, 397–408 (2015). https://doi.org/10.1007/s12031-015-0565-y

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