Chang Leah, Čok Zala, Yu Lei
Department of Genetics, Center of Alcohol & Substance Use Studies, Rutgers University, Piscataway, NJ 08854, USA.
Cells. 2025 Apr 11;14(8):577. doi: 10.3390/cells14080577.
Neuropathic pain is a chronic condition resulting from injury or dysfunction in the somatosensory nervous system, which leads to persistent pain and a significant impairment of quality of life. Research has highlighted the complex molecular mechanisms that underlie neuropathic pain and has begun to delineate the roles of microRNAs (miRNAs) in modulating pain pathways. miRNAs, which are small non-coding RNAs that regulate gene expression post-transcriptionally, have been shown to influence key cellular processes, including neuroinflammation, neuronal excitability, and synaptic plasticity. These processes contribute to the persistence of neuropathic pain, and miRNAs have emerged as critical regulators of pain behaviors by modulating signaling pathways that control pain sensitivity. miRNAs can influence neuropathic pain by targeting genes that encode protein kinases involved in pain signaling. This review focuses on miRNAs that have been demonstrated to modulate neuropathic pain behavior through their effects on protein kinases or their immediate upstream regulators. The relationship between miRNAs and neuropathic pain behaviors is characterized as either an upregulation or a downregulation of miRNA levels that leads to a reduction in neuropathic pain. In the case of miRNA upregulation resulting in an alleviation of neuropathic pain behaviors, protein kinases exhibit a positive correlation with neuropathic pain, whereas decreased protein kinase levels correlate with diminished neuropathic pain behaviors. The only exception is GRK2, which shows an inverse correlation with neuropathic pain. In the case of miRNA downregulation resulting in a reduction in neuropathic pain behaviors, protein kinases display mixed relationships to neuropathic pain, with some kinases exhibiting positive correlation, while others exhibit negative correlation. By exploring how protein kinases mediate miRNA modulation of neuropathic pain, valuable insight may be gained into the pathophysiology of neuropathic pain, offering potential therapeutic targets for developing more effective strategies for pain management.
神经性疼痛是一种由躯体感觉神经系统损伤或功能障碍引起的慢性疾病，会导致持续性疼痛并严重损害生活质量。研究突出了神经性疼痛背后复杂的分子机制，并已开始阐明微小RNA（miRNA）在调节疼痛通路中的作用。miRNA是一类小的非编码RNA，可在转录后调节基因表达，已被证明会影响关键的细胞过程，包括神经炎症、神经元兴奋性和突触可塑性。这些过程导致神经性疼痛持续存在，而miRNA已成为通过调节控制疼痛敏感性的信号通路来调节疼痛行为的关键调节因子。miRNA可通过靶向编码参与疼痛信号传导的蛋白激酶的基因来影响神经性疼痛。本综述重点关注已被证明通过对蛋白激酶或其直接上游调节因子的作用来调节神经性疼痛行为的miRNA。miRNA与神经性疼痛行为之间的关系表现为miRNA水平的上调或下调，进而导致神经性疼痛减轻。在miRNA上调导致神经性疼痛行为减轻的情况下，蛋白激酶与神经性疼痛呈正相关，而蛋白激酶水平降低与神经性疼痛行为减轻相关。唯一的例外是GRK2，它与神经性疼痛呈负相关。在miRNA下调导致神经性疼痛行为减少的情况下，蛋白激酶与神经性疼痛呈现出复杂的关系，一些激酶呈正相关，而另一些呈负相关。通过探索蛋白激酶如何介导miRNA对神经性疼痛的调节，可能会对神经性疼痛的病理生理学有宝贵的见解，为开发更有效的疼痛管理策略提供潜在的治疗靶点。
