Integrative Analysis of Hub Genes and miRNAs Reveals Inflammatory and Structural Signatures in Fibromyalgia and Their Modulation Following Manual Therapy

Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive dysfunction, with substantial impact on quality of life and functional capacity. Despite its high prevalence, its underlying molecular mechanisms remain incompletely understood, and reliable biomarkers are lacking. This study performed an integrative analysis of publicly available transcriptomic datasets combined with protein–protein interaction network analysis, hub gene identification, and investigation of microRNA (miRNA)-mediated posttranscriptional regulation, in addition to evaluating molecular modulation following therapeutic intervention. Differentially expressed genes consistently identified across independent cohorts revealed two major molecular axes: An inflammatory–immune axis involving cytokine and interferon-related pathways, including IL6 , TNF , CXCL8 , and STAT1 , and a structural axis associated with extracellular matrix organization, including COL1A1 , COL3A1 , FN1 , and ITGB1. Integration with miRNA data demonstrated reduced expression of regulatory miRNAs linked to inflammatory and structural pathways, suggesting impaired posttranscriptional control. Therapeutic modulation analysis further demonstrated reduced expression of inflammatory genes and increased expression of structural genes following manual therapy, indicating partial reversibility of these molecular alterations. Collectively, these findings support the presence of multilevel molecular dysregulation in fibromyalgia and highlight potential biomarkers and therapeutic targets associated with inflammatory and peripheral structural mechanisms.