Epigenetic mechanisms, particularly histone post-translational modifications (PTMs), are pivotal in regulating diverse biological processes, including inflammation and pain. Histone H3 is a crucial protein that significantly regulates gene expression following tissue injury-associated pain. Previously, we found that spinal Pdyn neurons contribute to burn injury-induced heat hyperalgesia via histone H3 phosphorylation-dependent signaling. We suspect that burn injury affects additional histone post-translational modifications beyond histone H3 phosphorylation at serine 10.In our study, we aimed to elucidate the impact of additional histone H3 post-translational modifications (PTMs) in the context of post-burn injury responses within the mouse spinal cord. To achieve this, we employed chip-grade antibodies in a Simple Western assay, a robust technique for protein analysis. In the spinal cord of mice, we observed elevated levels of histone H3 phosphorylation at serine 10, hypermethylation of histone H3 at lysine K4 (H3K4), and hyperacetylation of trimethylated variant of H3K4 at lysine K9.Furthermore, we explored the role of spinal Pdyn neurons in burn-induced nociception. Using a dual immunohistochemical method on spinal cord sections from mice, we obtained complementary evidence that supports our Simple Western assay findings. Our double immunofluorescence data directly highlights the critical involvement of Pdyn neurons in burn injury-evoked central sensitization and nociception in mice. Acknowledgment: “TKP2021-EGA-20 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme.”