Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.

中文翻译：

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用正电子发射断层扫描研究慢性腰痛的神经表观遗传改变。


表观遗传学作为分子改变的潜在介质引起了相当大的兴趣，这些改变可能是伤害感受器、神经元和神经胶质细胞响应各种环境刺激而长期致敏的基础。组蛋白乙酰化和脱乙酰化是调节染色质的关键过程，影响基因表达;组蛋白乙酰化升高增强了转录活性，而乙酰化降低导致 DNA 浓缩和基因抑制。在各种动物疼痛模型中检测到组蛋白脱乙酰酶 （HDAC） 水平的改变，HDAC 抑制剂在这些模型中显示出镇痛作用，表明 HDAC 参与慢性疼痛通路。然而，动物研究主要检查了疼痛诱导后脊髓内的表观遗传调节，这可能不能完全反映人类慢性疼痛的复杂性。此外，方法学的局限性以前阻碍了对人脑表观遗传变化的深入研究。在这项研究中，我们采用了 HDAC 选择性放射性示踪剂 [11C]Martinostat、正电子发射断层扫描来评估 23 名慢性腰痛 （cLBP） 患者和 11 名年龄匹配和性别匹配的对照患者大脑中 HDAC 的可用性。我们的数据显示，相对于对照组，cLBP 患者与疼痛处理相关的多个大脑区域中的 [11C] Martinostat 结合显着减少，突出了靶向 HDAC 调节作为 cLBP 治疗策略的前景广阔的潜力。