Nociception Group, Department of Surgery and Cancer, Division of Anaesthetics, Pain Medicine and Intensive Care, Chelsea and Westminster Hospital Campus, Imperial College London, 369 Fulham Road, London SW10 9FJ, UK.
Department of Brain Sciences, Division of Neuroscience, Imperial College London, E505, Burlington Danes, Du Cane Road, London W12 ONN, UK.
Int J Mol Sci. 2022 Jan 11;23(2):752. doi: 10.3390/ijms23020752.
While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.
虽然大约有一半的人口在其一生中经历与组织损伤相关的持续疼痛,但目前基于症状的方法往往无法将这种疼痛降低到令人满意的水平。为了提供更好的患者护理,必须开发基于机制的镇痛方法,这就需要全面了解导致与组织损伤相关的持续性疼痛的伤害性机制。导致神经系统中转录改变的表观遗传事件在组织损伤引起的疼痛维持中起着关键作用。然而,这些事件导致疼痛持续存在的机制尚不完全清楚。这篇综述总结和批判性地评估了两种表观遗传机制,即 DNA 甲基化和非编码 RNA 表达,在组织损伤相关疼痛发展过程中伤害性途径中转录调节中的作用。我们评估了临床前数据及其转化意义,并评估了控制 DNA 甲基化和非编码 RNA 表达作为新的镇痛方法和/或持续性疼痛生物标志物的潜力。