Circulating miRNA Response to Kinesiological Intervention in Runners with Musculoskeletal Pain: A Pilot Study Integrating Expression and Network Analysis

Background: Musculoskeletal pain is highly prevalent among runners and often im-pairs performance and quality of life. Exercise-based interventions, such as kinesiology-guided programs, are increasingly used to promote recovery and prevent recurrence; however, individual responses vary widely. Circulating miRNA may serve as molecular biomarkers to elucidate un-derlying mechanisms and predict therapeutic outcomes. This study aimed to assess changes in circulating miRNAs in runners following a kinesiology-based intervention and to explore their potential involvement in pain-related biological processes. Methods: Seventeen long-distance runners with musculoskeletal pain underwent a six-week ki-nesiology-based intervention. Pain intensity and physical activity were assessed pre- and post-intervention. Plasma levels of four inflammation- and muscle-related miRNAs (hsa-let-7a-5p, hsa-miR-133b, hsa-miR-146a-5p, and hsa-miR-155-5p) were quantified using qRT-PCR. Bioin-formatic analyses were conducted to explore molecular networks involving the most responsive miRNAs. Results: Among the four analyzed miRNAs, three showed a downregulation after the interven-tion, with a statistically significant reduction in hsa-let-7a-5p (p = 0.035) and a near-significant decrease in hsa-miR-133b (p = 0.068). No significant associations were found between miRNA changes and pain remission in regression analysis. However, integrative network and pathway analyses revealed the involvement of hsa-let-7a-5p and hsa-miR-133b in molecular pathways re-lated to inflammation, tissue remodeling, and neuroimmune signaling. Discussion: The observed modulation of hsa-let-7a-5p and hsa-miR-133b suggests that these miRNAs may be sensitive to physiological changes induced by kinesiological intervention, po-tentially reflecting systemic adaptations rather than directly mediating pain remission. The lack of correlation with pain reduction may be due to the small sample size or the multifactorial nature of pain modulation. Nonetheless, the bioinformatic evidence highlights plausible biological mechanisms that merit further investigation. Conclusions: These findings suggest that hsa-let-7a-5p and hsa-miR-133b may reflect biological adaptations to functional recovery, even if they are not predictive of clinical outcomes. Further research is needed to validate their role in musculoskeletal rehabilitation and to assess their po-tential utility in guiding personalized exercise-based strategies.