MicroRNAs as Biomarkers of Pain Intensity in Patients With Chronic Fatigue Syndrome.

Abstract

Numerous experimental models have shown that microRNAs (miRNAs)play an important role in regulating pain processing in clinical pain disorders. In this study, we evaluated a set of miRNAs as diagnostic biomarkers of pain intensity in adolescents with chronic fatigue syndrome (CFS). We then correlated the expression of these miRNAs with the levels of inflammatory markers and pain-related comorbidities in adolescents with CFS and healthy controls (HCs). A total of 150 adolescents, 12 to 18years of age, participated in this study between April 2016 and April 2017. The participants were classified into 2 groups: adolescents with CFS (n=100) and HCs (n=50). Reverse-transcription polymerase chain reaction was used to evaluate the expression of miR-558, miR-146a, miR-150, miR-124, and miR-143. Immunoassay analysis was used to assess the levels of immune inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Adolescents with CFS showed significantly higher pain thresholds than comparable nonfatigued HCs. Ability to enjoy life and relations with others were the parameters least influenced by pain in CFS patients. Differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143 was significantly downregulated and notably interfered with pain intensity and frequency in patients with CFS. Also, the expression of these miRNAs was significantly correlated with that of IL-6, TNF-α, and COX-2, which have been shown to mediate pain intensity in patients with CFS. Girls with CFS showed significantly decreased expression levels of these miRNAs compared with the levels of boys with CFS. Girls with CFS also showed increased expression of the inflammatory pain-related markers IL-6, TNF-α, and COX-2 compared with the levels of boys with CFS. The intensity and consequences of pain were influenced by differential expression of miR-558, miR-146a, miR-150, miR-124, and miR-143, which was directly associated with higher expression of the immune inflammatory-related genes TNFα, IL-6, and COX-2 in adolescents with CFS. Further studies of larger patient cohorts will help clarify the role of miRNAs in the pathogenesis of CFS.