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

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 ne...

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Published in:Nature communications 2023-11, Vol.14 (1), p.7234-7234, Article 7234
Main Authors: Tao, Yu, Zhang, Yuan, Jin, Xiaohong, Hua, Nan, Liu, Hong, Qi, Renfei, Huang, Zitong, Sun, Yufang, Jiang, Dongsheng, Snutch, Terrance P., Jiang, Xinghong, Tao, Jin
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Subjects:
13/95
14/32
38/91
42/89
45/15
631/378/2584/2585
631/378/2620/410
631/378/3917
64/86
Arcuate nucleus
Cerebrospinal fluid
Chromosome 3
Deacetylation
Endorphins
Epigenetics
Histone deacetylase
Histone H3
Histones
Humanities and Social Sciences
Hypothalamus
Lysine
MicroRNAs
miRNA
multidisciplinary
Neuralgia
Neurons
Pain
Pain perception
Pathogenesis
Proopiomelanocortin
Proprotein convertases
Regulatory mechanisms (biology)
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Synthesis
Therapeutic targets
Trigeminal nerve
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cited_by cdi_FETCH-LOGICAL-c518t-1861943a1871b75eaba4dc83b46bd35e7f4bee02ad0325d5496b8552ee6124473
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container_title Nature communications
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creator Tao, Yu
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Jiang, Xinghong
Tao, Jin
description 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. Neuropathic pain is a complex and often disabling condition with unclear pathogenesis. Here, the authors elucidate an epigenetic regulatory pathway driven by microRNA regulation of betaendorphin (β-EP) synthesis in the hypothalamic arcuate nucleus (ARC) neurons to modulate neuropathic pain.
doi_str_mv 10.1038/s41467-023-43022-7
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subjects 13/95
14/32
38/91
42/89
45/15
631/378/2584/2585
631/378/2620/410
631/378/3917
64/86
Arcuate nucleus
Cerebrospinal fluid
Chromosome 3
Deacetylation
Endorphins
Epigenetics
Histone deacetylase
Histone H3
Histones
Humanities and Social Sciences
Hypothalamus
Lysine
MicroRNAs
miRNA
multidisciplinary
Neuralgia
Neurons
Pain
Pain perception
Pathogenesis
Proopiomelanocortin
Proprotein convertases
Regulatory mechanisms (biology)
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Synthesis
Therapeutic targets
Trigeminal nerve
title Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model
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