The role of mast cells in migraine pathophysiology
Theoharis C. Theoharides, , Jill Donelan, Kristiana Kandere-Grzybowska1 and Aphrodite Konstantinidou2
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA
Accepted 30 November 2004. Available online 12 February 2005.
Mast cells are critical players in allergic reactions, but they have also been shown to be important in immunity and recently also in inflammatory diseases, especially asthma. Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells. These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation. Neuropeptides such as calcitonin gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate cyclase activating peptide (PACAP), and substance P (SP) activate mast cells leading to secretion of vasoactive, pro-inflammatory, and neurosensitizing mediators, thereby contributing to migraine pathogenesis. Brain mast cells can also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines. A better understanding of brain mast cell activation in migraines would be useful and could lead to several points of prophylactic intervention.
Keywords: Allergy; CRH; Histamine; Mast cells; Migraines; Stress
Abbreviations: BBB, blood–brain barrier; CGRP, calcitonin-gene related peptide; CRH, corticotropin-releasing hormone; IL-6, interleukin-6; NGF, nerve growth factor; NO, nitric oxide; NT, neurotensin; PACAP, pituitary adenylate cyclase activating peptide; SP, substance P; TNF-α, tumor necrosis factor-alpha; VIP, vasoactive intestinal peptide; Ucn, urocortin; VEGF, vascular endothelial growth factor
Neuroscience classification codes: Neural-immune interactions, Brain
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