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.
Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells.J Pharmacol Exp Ther. 2016 Mar;356(3):664-72. doi: 10.1124/jpet.115.230060. Epub 2016 Jan 13. J Pharmacol Exp Ther. 2016. PMID: 26763911 Free PMC article.
Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome.Clin Ther. 2019 Aug;41(8):1564-1574.e2. doi: 10.1016/j.clinthera.2019.05.019. Epub 2019 Jul 11. Clin Ther. 2019. PMID: 31303280 Clinical Trial.
Fibromyalgia--new concepts of pathogenesis and treatment.Int J Immunopathol Pharmacol. 2006 Jan-Mar;19(1):5-10. Int J Immunopathol Pharmacol. 2006. PMID: 16569342 Review.
Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle--A Microdialysis Study.PLoS One. 2015 Dec 1;10(12):e0143856. doi: 10.1371/journal.pone.0143856. eCollection 2015. PLoS One. 2015. PMID: 26624891 Free PMC article.
Impact of mast cells in fibromyalgia and low-grade chronic inflammation: Can IL-37 play a role?Dermatol Ther. 2020 Jan;33(1):e13191. doi: 10.1111/dth.13191. Epub 2019 Dec 26. Dermatol Ther. 2020. PMID: 31837249 Review.
Cited by 3 articles
T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives.Int J Mol Sci. 2020 Feb 11;21(4):1186. doi: 10.3390/ijms21041186. Int J Mol Sci. 2020. PMID: 32054062 Free PMC article. Review.
Restless legs syndrome is associated with mast cell activation syndrome.J Clin Sleep Med. 2020 Mar 15;16(3):401-408. doi: 10.5664/jcsm.8216. Epub 2020 Jan 14. J Clin Sleep Med. 2020. PMID: 31994488
Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation.Antioxidants (Basel). 2019 Dec 6;8(12):628. doi: 10.3390/antiox8120628. Antioxidants (Basel). 2019. PMID: 31817734 Free PMC article.