Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1

Fibromyalgia (FM), classified by ICD-11 with code MG30.0, is a chronic debilitating disease characterized by widespread pain, fatigue, cognitive impairment, sleep, and intestinal alterations, among others. FM affects a large proportion of the worldwide population, with increased prevalence among women. The lack of understanding of its etiology and pathophysiology hampers the development of effective treatments. Our group had developed a manual therapy (MT) pressure-controlled custom manual protocol on FM showing hyperalgesia/allodynia, fatigue, and patient's quality of life benefits in a cohort of 38 FM cases (NCT04174300). With the aim of understanding the therapeutic molecular mechanisms triggered by MT, this study interrogated Peripheral Blood Mononuclear Cell (PBMC) transcriptomes from FM participants in this clinical trial using whole RNA sequencing (RNAseq) and reverse transcription followed by quantitative Polymerase Chain Reaction (RT-qPCR) technologies. The results show that the salt-induced kinase SIK1 gene was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, this study compared the findings in a non-FM control cohort subjected to the same MT protocol, evidencing that those changes in SIK1 expression with MT only occurred in individuals with FM. This positions SIK1 as a potential biomarker to monitor response to MT and as a therapeutic target of FM, which will be further explored by continuation studies.