Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
Rutgers Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.
Exp Neurol. 2021 Mar;337:113572. doi: 10.1016/j.expneurol.2020.113572. Epub 2020 Dec 16.
Neuropathic pain is the most common clinical disorder destroying the quality of patient life and leading to a marked economic and social burden. Opioids are still last option for pharmacological treatment of this disorder, but their antinociceptive effects are limited in part due to the downregulation of opioid receptors in the primary afferent neurons after peripheral nerve trauma. How this downregulation occurs is not completely understood, but recent studies have demonstrated that peripheral nerve trauma drives the alterations in epigenetic modifications (including DNA methylation, histone methylation and mciroRNAs), expression of transcription factors, post-transcriptional modifications (e.g., RNA methylation) and protein translation initiation in the neurons of nerve trauma-related dorsal root ganglion (DRG) and that these alternations may be associated with nerve trauma-caused downregulation of DRG opioid receptors. This review presents how opioid receptors are downregulated in the DRG after peripheral nerve trauma, specifically focusing on distinct molecular mechanisms underlying transcriptional and translational processes. This review also discusses how this downregulation contributes to the induction and maintenance of neuropathic pain. A deeper understanding of these molecular mechanisms likely provides a novel avenue for prevention and/or treatment of neuropathic pain.
神经病理性疼痛是最常见的临床疾病，破坏患者的生活质量，并导致显著的经济和社会负担。阿片类药物仍然是治疗这种疾病的最后选择，但它们的镇痛作用是有限的，部分原因是外周神经损伤后初级传入神经元中阿片受体的下调。这种下调是如何发生的还不完全清楚，但最近的研究表明，外周神经损伤会导致神经元中表观遗传修饰（包括 DNA 甲基化、组蛋白甲基化和 microRNAs）、转录因子表达、转录后修饰（如 RNA 甲基化）和蛋白翻译起始的改变，与神经损伤相关的背根神经节（DRG）中的这些改变可能与 DRG 阿片受体的神经损伤引起的下调有关。这篇综述介绍了外周神经损伤后 DRG 中阿片受体如何下调，特别是重点介绍了转录和翻译过程背后的不同分子机制。本文还讨论了这种下调如何导致神经病理性疼痛的发生和维持。对这些分子机制的深入了解可能为预防和/或治疗神经病理性疼痛提供新的途径。
