MicroRNA circulating in the early aftermath of motor vehicle collision predict persistent pain development and suggest a role for microRNA in sex-specific pain differences.
MicroRNA circulating in the early aftermath of motor vehicle collision predict persistent pain development and suggest a role for microRNA in sex-specific pain differences.
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DOI：
10.1186/s12990-015-0069-3
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发表时间：
2015-10-24
期刊：
影响因子：
3.3
通讯作者：
McLean SA
中科院分区：
文献类型：
--
作者：
Linnstaedt SD;Walker MG;Parker JS;Yeh E;Sons RL;Zimny E;Lewandowski C;Hendry PL;Damiron K;Pearson C;Velilla MA;O'Neil BJ;Jones J;Swor R;Domeier R;Hammond S;McLean SA
在机动车碰撞（MVC）等常见应激暴露后，影响从急性到持续性肌肉骨骼疼痛转变的分子介质仍然知之甚少。在这项探索性的概念验证研究中，我们比较了MVC早期发生和未发生持续性疼痛的个体的循环microRNA （miRNA）表达谱。血液RNA样本来自非裔美国人（n = 53），他们在MVC后到急诊室就诊，评估后出院回家。在MVC后疼痛发生的最常见和最病态的轴区存在或不存在严重疼痛，在MVC后6周通过标准化问卷进行评估。采用miRNA测序法检测miRNA表达；非参数分析用于比较有和无持续性疼痛个体的miRNA表达水平。6周时，32个成熟miRNA在有和没有严重轴向疼痛的患者中差异表达（p < 0.05）。miR-135a-5p是一种已知具有应激反应的血清素受体调节剂，在两组之间差异最显著（p = 3 × 10−4）。在这个小样本中，该miRNA和miR-3613-3p （p = 0.001）在多次检验（FDR = 0.15）校正后存活。有趣的是，X染色体定位富集了差异表达的miRNA。在二级分析中，8个X染色体miRNA (a)与女性轴性疼痛的相关性高于男性，(b)在女性外周血中的表达高于男性，以及(c)在通路分析（DIANA miRPath v 2.0）中预测调节先前涉及各种疼痛病理的神经元和神经内分泌通路。这些结果表明，循环miRNA预测MVC后持续严重的轴向疼痛，并提示它们可能参与创伤后肌肉骨骼疼痛的发病机制。然而，需要进一步的研究来确定这些miRNA是否起直接的因果作用。本文的在线版本（doi:10.1186/s12990-015-0069-3）包含补充材料，可供授权用户使用。
Molecular mediators influencing the transition from acute to persistent musculoskeletal pain following common stress exposures such as motor vehicle collision (MVC) remain poorly understood. In this exploratory, proof of concept study, we compared circulating microRNA (miRNA) expression profiles in the early aftermath of MVC among individuals who did and did not subsequently develop persistent pain. Blood RNA samples were obtained from African American individuals (n = 53) who presented to the emergency department after MVC and were discharged to home after evaluation. The presence or absence of severe pain in the axial region, the most common and morbid region in which post-MVC pain occurs, was assessed 6 weeks following MVC via standardized questionnaire. miRNA expression was determined using miRNA-sequencing; nonparametric analyses were used to compare miRNA expression levels among individuals with and without persistent pain. Thirty-two mature miRNA were differentially expressed (p < 0.05) in those with and without severe axial pain at 6 weeks. miR-135a-5p, a regulator of the serotonin receptor that is known to be stress-responsive, differed most significantly between groups (p = 3 × 10−4). This miRNA, and miR-3613-3p (p = 0.001) survived correction for multiple testing (FDR = 0.15) in this small sample. Interestingly, differentially expressed miRNA were enriched for X chromosome location. In secondary analyses, the eight X chromosome miRNA were (a) more significantly associated with axial pain in women than men, (b) expressed more highly in the peripheral blood of women than men, and (c) predicted in pathway analyses (DIANA miRPath v 2.0) to regulate neuronal and neuroendocrine pathways previously implicated in various pain pathologies. These results show that circulating miRNA predict persistent severe axial pain after MVC and suggest that they may be involved in the pathogenesis of post-traumatic musculoskeletal pain. However, further studies are needed to determine if these miRNA play a direct causal role. The online version of this article (doi:10.1186/s12990-015-0069-3) contains supplementary material, which is available to authorized users.