Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
J Transl Med. 2011 Nov 10;9:195. doi: 10.1186/1479-5876-9-195.
Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification.
We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions.
Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs.
miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.
小非编码 RNA（miRNA）的异常表达是几种人类疾病的共同特征。本研究的目的是鉴定复杂区域疼痛综合征（CRPS）患者的 miRNA 调节，CRPS 是一种由中枢和/或外周神经系统功能障碍引起的慢性疼痛病症。由于多种引发病变、症状和治疗条件，CRPS 患者群体非常多样化。我们的目标是鉴定血液中差异表达的 miRNA，并探索其在患者分层中的应用。
我们使用 TaqMan 低密度阵列卡对 41 例 CRPS 患者和 20 例对照者的全血 miRNA 进行了分析。由于已知神经源性炎症在 CRPS 中起重要作用，我们测量了来自同一个体的血液中的炎症标志物，包括趋化因子、细胞因子及其可溶性受体。对 miRNA、炎症标志物和其他参数（包括疾病症状、药物和合并症）进行了相关性分析。
从 miRNA 分析中出现了三组不同的患者。一组由 60%的 CRPS 患者组成，无对照者。其余患者的 miRNA 图谱在另外两组中穿插在对照样本中。我们鉴定了 CRPS 患者中 18 个 miRNA 的差异表达。炎症标志物分析显示，血管内皮生长因子（VEGF）、白细胞介素 1 受体拮抗剂（IL1Ra）和单核细胞趋化蛋白 1（MCP1）在 CRPS 患者中显著升高。VEGF 和 IL1Ra 与患者报告的疼痛水平呈显著相关性。根据 miRNA 图谱对聚类的患者进行分析，在总患者群体中发现的相关性没有统计学意义。对血液中检测到的 miRNA 与其他参数的相关性分析鉴定了与偏头痛、甲状腺疾病以及使用麻醉剂和抗癫痫药物等合并症相关的 miRNA。
miRNA 图谱可用于患者分层，具有作为疼痛潜在生物标志物的潜力。差异表达的 miRNA 可以提供基因调控的分子见解，并可能为 CRPS 提供新的治疗干预策略。
