Department of Anesthesia and Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC, H3A 0G1, Canada.
School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA.
Trends Neurosci. 2018 Feb;41(2):100-114. doi: 10.1016/j.tins.2017.11.006.
Persistent pain, which is poorly treated and estimated to afflict one third of the world's population, is largely mediated by the sensitization of nociceptive neurons. This sensitization involves de novo gene expression to support biochemical and structural changes required to maintain amplified pain signaling that frequently persists even after injury to tissue resolves. While transcription-dependent changes in gene expression are important, recent work demonstrates that activity-dependent regulation of mRNA translation is key to controlling the cellular proteome and the development and maintenance of persistent pain. In this review, we highlight recent advances in translational regulation of gene expression in nociceptive circuits, with a focus on key signaling pathways and mRNA targets that may be tractable for the creation of next-generation pain therapeutics.
持续性疼痛是一种治疗效果不佳的疾病，据估计全球有三分之一的人口受其影响，它主要是由伤害性神经元的敏化所介导的。这种敏化涉及新基因的表达，以支持维持放大的疼痛信号所需的生化和结构变化，而这种放大的疼痛信号即使在组织损伤消退后也经常持续存在。虽然转录依赖性的基因表达变化很重要，但最近的研究表明，mRNA 翻译的活性依赖性调节是控制细胞蛋白质组以及持续性疼痛的发生和维持的关键。在这篇综述中，我们重点介绍了伤害性回路中转录后基因表达调控的最新进展，特别是可能适用于新一代疼痛治疗药物开发的关键信号通路和 mRNA 靶点。
