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 wide-spread pain, fatigue, cognitive impairment, sleep and intestinal alterations, among other. FM affects a large proportion of the world-wide 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 PBMC transcriptomes from FM participants of this clinical trial using RNAseq and RT-qPCR technologies. The results showed that the salt-induced kinase SIK1 gene was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, the study compared the findings in a non-FM control cohort subjected to the same MT protocol evidencing that 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, to be further explored by continuation studies. Keywords: fibromyalgia; myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); pressure point threshold (PPT); physiotherapy; manual therapy (MT); NCT04174300; SIK1 Overall design: Transcriptome evaluation of PBMCs from fibromyalgia patients after (post-) manual therapy with respect to basal values (pre-)