Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2022 Mar 15;23(6):3178. doi: 10.3390/ijms23063178.
Burn injury is a trauma resulting in tissue degradation and severe pain, which is processed first by neuronal circuits in the spinal dorsal horn. We have recently shown that in mice, excitatory dynorphinergic (Pdyn) neurons play a pivotal role in the response to burn-injury-associated tissue damage via histone H3.1 phosphorylation-dependent signaling. As Pdyn neurons were mostly associated with mechanical allodynia, their involvement in thermonociception had to be further elucidated. Using a custom-made AAV9_mutH3.1 virus combined with the CRISPR/cas9 system, here we provide evidence that blocking histone H3.1 phosphorylation at position serine 10 (S10) in spinal Pdyn neurons significantly increases the thermal nociceptive threshold in mice. In contrast, neither mechanosensation nor acute chemonociception was affected by the transgenic manipulation of histone H3.1. These results suggest that blocking rapid epigenetic tagging of S10H3 in spinal Pdyn neurons alters acute thermosensation and thus explains the involvement of Pdyn cells in the immediate response to burn-injury-associated tissue damage.
烧伤是一种导致组织退化和剧烈疼痛的创伤，首先由脊髓背角的神经元回路处理。我们最近表明，在小鼠中，兴奋性强啡肽能（Pdyn）神经元通过组蛋白 H3.1 磷酸化依赖性信号在与烧伤相关的组织损伤的反应中起关键作用。由于 Pdyn 神经元主要与机械性痛觉过敏有关，因此必须进一步阐明它们在热痛觉中的参与。使用定制的 AAV9_mutH3.1 病毒结合 CRISPR/cas9 系统，我们在这里提供的证据表明，阻断脊髓 Pdyn 神经元中组蛋白 H3.1 丝氨酸 10（S10）的磷酸化显著增加了小鼠的热痛觉阈值。相比之下，组蛋白 H3.1 的转基因操作既不影响机械感觉，也不影响急性化学感觉过敏。这些结果表明，阻断脊髓 Pdyn 神经元中 S10H3 的快速表观遗传标记改变了急性热感觉，从而解释了 Pdyn 细胞在与烧伤相关的组织损伤的即刻反应中的参与。
