The p38/MK2 Axis in Monocytes of Fibromyalgia Syndrome Patients: An Explorative Study, 2021, Nugraha,Scheibe et al

[Sly Saint]

Abstract
Background and Objectives: The aetiology and pathomechanism of fibromyalgia syndrome 12 (FMS) as one of chronic pain syndromes still need to be further elucidated. Mitogen-activated protein kinase (MAPK) pathway has been proposed as a novel approach in pain management.

Since the major symptom of fibromyalgia syndrome (FMS) patients is pain, it became of interest whether MAPK pathways, such as the stress-activated p38 MAPK/MK2 axis, are activated in FMS patients. Therefore, this study aimed at determining p38 MAPK/MK2 in FMS patients.

Materials and Methods: Phosphorylation of MAPK-activated protein kinases 2 (MK2), a direct target of p38 MAPK, was measured in monocytes of FMS and healthy controls (HCs) to monitor the activity of this pathway.

Results: The mean level of phosphorylated MK2 was fivefold higher in FMS patients as compared to HCs (p < 0.001). Subgroup analysis revealed that antidepressants did not influence the activity of MK2 in FMS patients.

Conclusions: This result indicates that the p38/MK2 pathway could be involved in the pathomechanism of FMS, could act as a clinical marker for FMS, and could be a possible target for pain management in FMS patients.

https://www.mdpi.com/1648-9144/57/4/396

 

[Hutan]

To investigate whether activation of the p38 MAPK-MK2 pathway in monocytes could act as a critical mediator for FMS patients, our approach was to compare phosphorylation of p38 MAPK substrate, MK2, in blood monocytes of FMS patients and healthy subjects. Our hypothesis was that the level of MK2 might be altered in FMS patients because of its stress-dependent activation and its role in pain-related mechanisms.

The starting point and the wrapping of this study is that fibromyalgia is the result of stress. The arguments for that are weak, with the issues including the validity of the assessment of depression in people with a debilitating chronic illness and with pain. And this study did not find a relationship between their chosen biomarker and depression, although it's a bit murky.

However, in this study, a clear correlation between MK2 activity and depression in FMS patients could not be observed.

Setting all that aside, the biological finding of an increase in the MK2 molecule in this small study is interesting, suggesting that fibromyalgia may be some sort of inflammatory condition.

In addition, the p38 MAPK pathway is activated under inflammatory and neuropathic pain conditions, and activated kinases of this pathway can be used as molecular and cellular markers for pain conditions [13]. Inhibition of p38 MAPK is effective to reduce rheumatoid arthritis activity and inflammatory pain [14,15]. The p38 MAPK inhibitor dilmapimod significantly reduced neuropathic pain