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Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model.
Nat. Commun. 14:7234 (2023)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Rat Model; Histone Acetylation; Trigeminal Ganglion; Expression; Accumbens; Chromatin; System; Stress; Hypersensitivity; Involvement
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Zeitschrift
Nature Communications
Quellenangaben
Band: 14,
Heft: 1,
Artikelnummer: 7234
Verlag
Nature Publishing Group
Verlagsort
London
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Regenerative Biology and Medicine (IRBM)
Förderungen
MOE Key Laboratory of Geriatric Diseases and Immunology - Priority Academic Program Development of Jiangsu Higher Education Institutions
Practice Innovation Program of Jiangsu Province
Postgraduate Research amp
Project of State Key Laboratory of Radiation Medicine and Protection
Jiangsu Key Laboratory of Neuropsychiatric Diseases
Science and Technology Bureau of Suzhou
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
This study was supported by the National Natural Science Foundation of China (82371218, 82271245, and 82071236), the Natural Science Foundation of Jiangsu Province (BK20211073), the Science and Technology Bureau of Suzhou (SYS2020129), the Jiangsu Key Lab
Practice Innovation Program of Jiangsu Province
Postgraduate Research amp
Project of State Key Laboratory of Radiation Medicine and Protection
Jiangsu Key Laboratory of Neuropsychiatric Diseases
Science and Technology Bureau of Suzhou
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
This study was supported by the National Natural Science Foundation of China (82371218, 82271245, and 82071236), the Natural Science Foundation of Jiangsu Province (BK20211073), the Science and Technology Bureau of Suzhou (SYS2020129), the Jiangsu Key Lab