Epigenetic Regulation and Molecular Mechanisms of Burn Injury-Induced Nociception in the Spinal Cord of Mice

Autor: Zoltán Mészár, Virág Erdei, Péter Szücs, Angelika Varga
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 25, Iss 15, p 8510 (2024)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms25158510
Popis: Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and formalin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.
Databáze: Directory of Open Access Journals
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