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| Status |
Public on Oct 17, 2023 |
| Title |
Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model |
| Organism |
Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, although the underlying regulatory mechanisms remain unknown. Here, we elucidated a novel epigenetic pathway driven by microRNA regulation of beta-endorphin 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, histone deacetylase 9 downregulation increased acetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter increasing miR-203a-3p expression following nerve injury. 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. Our findings highlight an epigenetic regulatory pathway for β-EP synthesis that contributes to neuropathic pain development and maintenance mechanisms providing for new therapeutic targets for neuropathic pain treatment.
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| Overall design |
Hypothalamic arcuate nucleus miRNA profiles in rat ARC tissue on day 14 after CCI-ION (n=3) or sham operation (n=3)
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| Web link |
https://www.nature.com/articles/s41467-023-43022-7
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| |
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| Contributor(s) |
Tao Y, Tao J |
| Citation(s) |
37945654 |
| |
| Submission date |
Nov 01, 2022 |
| Last update date |
Nov 19, 2023 |
| Contact name |
Jin Tao |
| E-mail(s) |
taoj@suda.edu.cn
|
| Organization name |
Soochow University
|
| Department |
Physiology and Neurobiology
|
| Street address |
199 Ren-Ai Road
|
| City |
Suzhou |
| State/province |
Jiangsu |
| ZIP/Postal code |
215123 |
| Country |
China |
| |
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| Platforms (1) |
| GPL24688 |
HiSeq X Ten (Rattus norvegicus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA896478 |
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