In this review, we highlight the distinctive role of specific HDAC subtypes in a cell-specific manner in pain nociception, and outline the recent experimental evidence supporting the therapeutic potential of HDACi in neuropathic pain.
We have summarized studies of HDAC in neuropathic pain in Pubmed.
HDACs, widely distributed in the neuronal and non-neuronal cells of the dorsal root ganglion and spinal cord, regulate gene expression by deacetylation of histone or non-histone proteins and involving in increased neuronal excitability and neuroinflammation, thus promoting peripheral and central sensitization. Importantly, pharmacological manipulation of aberrant acetylation using HDAC-targeted inhibitors (HDACi) has shown promising pain-relieving properties in various preclinical models of neuropathic pain. Yet, many of which exhibit low-specificity that may induce off-target toxicities, underscoring the necessity for the development of isoform-selective HDACi in pain management.
Abnormally elevated HDACs promote neuronal excitability and neuroinflammation by epigenetically modulating pivotal gene expression in neuronal and immune cells, contributing to peripheral and central sensitization in the progression of neuropathic pain, and HDACi showed significant efficacy and great potential for alleviating neuropathic pain.
目的:在这篇综述中,我们强调了特定HDAC亚型在疼痛伤害感受中以细胞特异性方式的独特作用,并概述了最近的实验证据支持HDACi在神经性疼痛中的治疗潜力。
方法:我们总结了HDAC在Pubmed神经病理性疼痛中的研究。
结果:HDAC,广泛分布在背根神经节和脊髓的神经元和非神经元细胞中,通过组蛋白或非组蛋白的去乙酰化调节基因表达,并参与增加的神经元兴奋性和神经炎症,从而促进外周和中枢致敏。重要的是,在神经性疼痛的各种临床前模型中,使用HDAC靶向抑制剂(HDACi)对异常乙酰化的药理学操作显示出有希望的疼痛缓解特性.然而,其中许多表现出低特异性,可能诱导脱靶毒性,强调在疼痛管理中开发同工型选择性HDACi的必要性。
结论:异常升高的HDAC通过表观遗传调节神经元和免疫细胞中关键基因的表达促进神经元兴奋性和神经炎症,在神经性疼痛的进展中有助于外周和中枢敏化,和HDACi显示出显著的疗效和缓解神经性疼痛的巨大潜力。