Manual Therapy Improves Fibromyalgia Symptoms by Downregulating SIK1, 2024, Bonastre-Férez et al

Abstract

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.

Open access, https://www.mdpi.com/1422-0067/25/17/9523#B18-ijms-25-09523

 

"Furthermore, since our previous work, in the context of clinical trial NCT04174300, identified differences in response to MT among FM patients co-diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [18], we reassessed our RT-qPCR results, taking into account whether or not patients with FM had also received the ME/CFS diagnostic (Supplementary Table S1). The results indeed point out that the FM group with ME/CFS co-diagnosis (n = 19) does not seem to respond to MT by increasing their CX3CR1 levels, while DE of HBEGF and EGR2 appears more related to this group (Figure 6). EREG and SIK1 DE seem to specifically associate with both patient groups, without changes in the control non-FM group (Figure 5)."

Ref 18 is to the study discussed here, Pressure Point Threshold and ME/CFS comorbidity as Indicators of Physiotherapy Response in Fibromyalgia. Falaguera-Vera et al. 2020

 

Could be an interesting finding, but my first impression is that it's an association of no import. Also, in the conclusion the data's main function is to support the therapeutic efficacy of MT, manual pressure point massage therapy, their product/procedure.


I find that tender points (which were developed as a diagnostic marker for clinical FM research but no longer used in diagnosis since 2016) are quite variable in both location and pain intensity. The standardized layout of tender points does not always apply to the individual w/FM. New ones develop as pain spreads to additional body areas as the years pass.

Also, there is a huge variation in response to a pressure stimulus, depending on the level of FM symptom activation at that moment.

For instance, my mornings tend toward low FM pain, but my late afternoons are always a high pain level. Testing would have to include both early and late in the day sessions, and what about a two-week flare-up as occurs randomly?

And so, the subjects may have had mild FM, because they came in twice a week for 4 weeks.

The emphasis placed by the researchers on their pet project/technique of MT therapy (as evidenced by past published research), leads me to point out that any hands-on therapy gives only minutes of pain relief. It is a temporary distraction.

FM is a serious chronic pain condition and requires medication to lessen pain to a clinically significant degree---which is at least a 50-60% reduction of pain.