Abstract
Background: Migraine is a disabling neurological disorder where the release of neuropeptides and a local and systemic proinflammatory state prevail. MicroRNAs (miRs) are epigenetic regulators that control the expression of genes involved in inflammation, neovascularization, and pain-related processes. Cytokines mediate the inflammatory state, while miRs can modulate their expression. Methods: This is an analytical and observational study in which subjects with a diagnosis of chronic and episodic migraine and healthy controls were recruited, and the migraine patients were classified by episodic or chronic migraine, as well as with or without aura. Cytokines were measured using the ELISA technique, and the microRNAs hsa-miR-197-3p, hsa-miR-101-3p, and hsa-miR-143-3p were evaluated using qPCR methodology. We also utilized bioinformatic tools, such as miRBase, TargetScan, miRNet, and miRPath, to analyze the interactions and pathways involved. Results: Our findings revealed that hsa-miR-197-3p is elevated in patients without aura (29.91 ± 11.14 with aura vs. 81.10 ± 53.85 without aura, RU; p = 0.021), whereas hsa-miR-143-3p is elevated in episodic migraine (0.0639 ± 0.0227 in EM vs. 0.0308 ± 0.0174, RU p = 0.011). Furthermore, we found higher levels of IL-17 (9.46 ± 1.06 in CM vs. 7.61 ± 2.12 in EM, p = 0.030), IL-6 (4.95 ± 2.84 in CM vs. 1.52 ± 0.98 non-migraine subjects, p = 0.016), and TNFα in chronic migraine patients (0.46 ± 0.24 in CM vs. 0.20 ± 0.05 in non-migraine, p = 0.011 and vs. 0.20 ± 0.13 in EM, p = 0.016). Conclusions: Inflammation is present in migraine regardless of the clinical characteristics of the patients, although it may be accentuated in chronic migraine. Our preliminary findings suggest a potential role for peripheral inflammatory markers, including specific microRNAs (miR-197, miR-101, and miR-143) and cytokines (TNF-α, IL-6, and IL-17A), in the pathophysiology of migraine. These results, although limited by sample size and cross-sectional design, highlight molecular pathways that warrant further investigation.