Ciszek Brittney P, Khan Asma A, Dang Hong, Slade Gary D, Smith Shad, Bair Eric, Maixner William, Zolnoun Denniz, Nackley Andrea G
Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC.
Cystic Fibrosis Center, University of North Carolina, Chapel Hill, NC.
Transl Res. 2015 Dec;166(6):706-720.e11. doi: 10.1016/j.trsl.2015.06.008. Epub 2015 Jun 24.
Chronic pain is a significant health care problem, ineffectively treated because of its unclear etiology and heterogeneous clinical presentation. Emerging evidence demonstrates that microRNAs (miRNAs) regulate the expression of pain-relevant genes, yet little is known about their role in chronic pain. Here, we evaluate the relationship among pain, psychological characteristics, plasma cytokines, and whole blood miRNAs in 22 healthy controls (HCs); 33 subjects with chronic pelvic pain (vestibulodynia, VBD); and 23 subjects with VBD and irritable bowel syndrome (VBD + IBS). VBD subjects were similar to HCs in self-reported pain, psychological profiles, and remote bodily pain. VBD + IBS subjects reported decreased health and function; and an increase in headaches, somatization, and remote bodily pain. Furthermore, VBD subjects exhibited a balance in proinflammatory and anti-inflammatory cytokines, whereas VBD + IBS subjects failed to exhibit a compensatory increase in anti-inflammatory cytokines. VBD subjects differed from controls in expression of 10 miRNAs of predicted importance for pain and estrogen signaling. VBD + IBS subjects differed from controls in expression of 11 miRNAs of predicted importance for pain, cell physiology, and insulin signaling. miRNA expression was correlated with pain-relevant phenotypes and cytokine levels. These results suggest that miRNAs represent a valuable tool for differentiating VBD subtypes (localized pain with apparent peripheral neurosensory disruption vs widespread pain with a central sensory contribution) that may require different treatment approaches.
慢性疼痛是一个重大的医疗保健问题，由于其病因不明和临床表现异质性而难以得到有效治疗。新出现的证据表明，微小RNA（miRNA）可调节疼痛相关基因的表达，但人们对其在慢性疼痛中的作用知之甚少。在此，我们评估了22名健康对照者（HC）、33名患有慢性盆腔疼痛（前庭痛，VBD）的受试者以及23名患有VBD和肠易激综合征（VBD + IBS）的受试者的疼痛、心理特征、血浆细胞因子和全血miRNA之间的关系。VBD受试者在自我报告的疼痛、心理状况和远程身体疼痛方面与HC相似。VBD + IBS受试者报告健康和功能下降；头痛、躯体化和远程身体疼痛增加。此外，VBD受试者在促炎细胞因子和抗炎细胞因子之间表现出平衡，而VBD + IBS受试者未能表现出抗炎细胞因子的代偿性增加。VBD受试者与对照组相比，在预测对疼痛和雌激素信号传导具有重要意义的10种miRNA的表达上存在差异。VBD + IBS受试者与对照组相比，在预测对疼痛、细胞生理学和胰岛素信号传导具有重要意义的11种miRNA的表达上存在差异。miRNA表达与疼痛相关表型和细胞因子水平相关。这些结果表明，miRNA是区分VBD亚型（伴有明显外周神经感觉破坏的局部疼痛与伴有中枢感觉作用的广泛疼痛）的有价值工具，这两种亚型可能需要不同的治疗方法。
