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Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model

Author

Listed:
  • Yu Tao

    (Suzhou Medical College of Soochow University)

  • Yuan Zhang

    (The Second Affiliated Hospital of Soochow University
    Soochow University)

  • Xiaohong Jin

    (The First Affiliated Hospital of Soochow University)

  • Nan Hua

    (Suzhou Medical College of Soochow University)

  • Hong Liu

    (The First Affiliated Hospital of Soochow University)

  • Renfei Qi

    (Suzhou Medical College of Soochow University)

  • Zitong Huang

    (Suzhou Medical College of Soochow University)

  • Yufang Sun

    (Suzhou Medical College of Soochow University
    Soochow University)

  • Dongsheng Jiang

    (Helmholtz Zentrum München)

  • Terrance P. Snutch

    (University of British Columbia)

  • Xinghong Jiang

    (Suzhou Medical College of Soochow University
    Soochow University)

  • Jin Tao

    (Suzhou Medical College of Soochow University
    Soochow University)

Abstract

Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.

Suggested Citation

  • Yu Tao & Yuan Zhang & Xiaohong Jin & Nan Hua & Hong Liu & Renfei Qi & Zitong Huang & Yufang Sun & Dongsheng Jiang & Terrance P. Snutch & Xinghong Jiang & Jin Tao, 2023. "Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43022-7
    DOI: 10.1038/s41467-023-43022-7
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    References listed on IDEAS

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    3. Shelley L. Berger, 2007. "The complex language of chromatin regulation during transcription," Nature, Nature, vol. 447(7143), pages 407-412, May.
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