Migraine: Possible Role of Shear-Induced Platelet Aggregation With Serotonin Release

Authors


  • Conflict of Interest: The authors report no conflict of interest.

  • There was no financial support other than from our university.

P. Borgdorff, Laboratory for Physiology, VUMC, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands, email: p.borgdorff@vumc.nl

Abstract

Background.— Migraine patients are at an increased risk for stroke, as well as other thromboembolic events. This warrants further study of the role of platelets in a proportion of migraine patients.

Objective.— To extend the “platelet hypothesis” using literature data and observations made in a rat model of shear stress-induced platelet aggregation. Such aggregation causes release of serotonin, leading to vasoconstriction during sufficiently strong aggregation and to long-lasting vasodilation when aggregation diminishes. This vasodilation also depends on nitric oxide and prostaglandin formation.

Results.— A role for platelet aggregation in a number of migraineurs is indicated by reports of an increased platelet activity during attacks and favorable effects of antiplatelet medication. We hypothesize that in those patients, a migraine attack with or without aura may both be caused by a rise in platelet-released plasma serotonin, albeit at different concentration. At high concentrations, serotonin may cause vasoconstriction and, consequently, the neuronal signs of aura, whereas at low concentrations, it may already stimulate perivascular pain fibers and cause vasodilation via local formation of nitric oxide, prostaglandins, and neuropeptides. Platelet aggregation may be unilaterally evoked by elevated shear stress in a stenotic cervico-cranial artery, by reversible vasoconstriction or by other cardiovascular abnormality, eg, a symptomatic patent foramen ovale. This most likely occurs when a migraine trigger has further enhanced platelet aggregability; literature shows that many triggers either stimulate platelets directly or reduce endogenous platelet antagonists like prostacyclin.

Conclusion.— New strategies for migraine medication and risk reduction of stroke are suggested.

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