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. 2019 Aug 2;13:353.
doi: 10.3389/fncel.2019.00353. eCollection 2019.

Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome

Free PMC article

Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome

Theoharis C Theoharides et al. Front Cell Neurosci. .
Free PMC article


Fibromyalgia Syndrome (FMS) is a disorder of chronic, generalized muscular pain, accompanied by sleep disturbances, fatigue and cognitive dysfunction. There is no definitive pathogenesis except for altered central pain pathways. We previously reported increased serum levels of the neuropeptides substance P (SP) and its structural analogue hemokinin-1 (HK-1) together with the pro-inflammatory cytokines IL-6 and TNF in FMS patients as compared to sedentary controls. We hypothesize that thalamic mast cells contribute to inflammation and pain, by releasing neuro-sensitizing molecules that include histamine, IL-1β, IL-6 and TNF, as well as calcitonin-gene related peptide (CGRP), HK-1 and SP. These molecules could either stimulate thalamic nociceptive neurons directly, or via stimulation of microglia in the diencephalon. As a result, inhibiting mast cell stimulation could be used as a novel approach for reducing pain and the symptoms of FMS.

Keywords: IL-1 beta; IL-6); fibromyalgia syndrome; mast cells; neuroinflammation; pain; proinflammatory cytokines (TNF-alpha.


Diagram depicting the involvement of mast cells in the generation of pain in FMS. Mast cells (violet color) in the thalamus secrete pro-inflammatory and neuro-sensitizing mediators (CRH, histamine, IL-6, HK-1, SP, TNF, Tryptase). These mediators can then activate either microglia in thalamic nuclei or ascending nociceptive tracks creating the sensation of pain. Possible natural molecules to inhibit stimulated mast cells and/or microglia are flavonoids such as luteolin or tetramethoxyluteolin (Methlut).

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