PDF(Pubmed)
Abstract：
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.
摘要：
表观遗传机制，包括组蛋白翻译后修饰（PTM），在调节疼痛感知和烧伤的病理生理中起关键作用。然而,烧伤引起的疼痛的表观遗传调控和分子机制仍未得到充分探索。脊髓运动障碍（Pdyn）神经元通过p-S10H3依赖性信号传导导致严重烫伤型烧伤引起的热痛觉过敏。除p-S10H3外，烧伤可能会影响各种其他组蛋白H3PTM。双重免疫荧光染色和组蛋白H3蛋白分析显示，脊髓内H3K4me1和H3K4me3位点处有显著的超甲基化和S10H3处的过度磷酸化。通过分析脊髓背角的Pdyn神经元，我们发现了染色质激活的证据,p-S10H3免疫反应性显著升高.我们使用RNA-seq分析来比较烧伤和福尔马林诱导的炎性疼痛对脊髓转录组的影响。我们确定了98个DEGs用于烧伤，86个DEGs用于福尔马林诱导的炎性疼痛。有限数量的共享差异表达基因（DEGs）表明烧伤和福尔马林模型之间不同的中枢疼痛处理机制。KEGG通路分析支持这种差异，与烧伤激活Wnt信号。这项研究增强了我们对烧伤机制的理解，并揭示了不同起源的疼痛模型中收敛和发散的途径。
