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DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

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Listed:
  • Jian-Yuan Zhao

    (New Jersey Medical School, Rutgers, The State University of New Jersey
    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University)

  • Lingli Liang

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Xiyao Gu

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Zhisong Li

    (New Jersey Medical School, Rutgers, The State University of New Jersey
    The First Affiliated Hospital of Zhengzhou University)

  • Shaogen Wu

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Linlin Sun

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Fidelis E. Atianjoh

    (New Jersey Medical School, Rutgers, The State University of New Jersey
    College of Medicine, Howard University)

  • Jian Feng

    (Icahn School of Medicine at Mount Sinai)

  • Kai Mo

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Shushan Jia

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Brianna Marie Lutz

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Alex Bekker

    (New Jersey Medical School, Rutgers, The State University of New Jersey)

  • Eric J. Nestler

    (Icahn School of Medicine at Mount Sinai)

  • Yuan-Xiang Tao

    (New Jersey Medical School, Rutgers, The State University of New Jersey
    The First Affiliated Hospital of Zhengzhou University
    Pharmacology & Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey)

Abstract

Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent potassium (Kv) channel subunit Kcna2 promoter region and rescues Kcna2 expression in the injured DRG and attenuates neuropathic pain. Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads to spinal cord central sensitization and neuropathic pain symptoms. These findings suggest that DNMT3a may contribute to neuropathic pain by repressing Kcna2 expression in the DRG.

Suggested Citation

  • Jian-Yuan Zhao & Lingli Liang & Xiyao Gu & Zhisong Li & Shaogen Wu & Linlin Sun & Fidelis E. Atianjoh & Jian Feng & Kai Mo & Shushan Jia & Brianna Marie Lutz & Alex Bekker & Eric J. Nestler & Yuan-Xia, 2017. "DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14712
    DOI: 10.1038/ncomms14712
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