Prostaglandin-E 2 levels over the course of glyceryl trinitrate provoked migraine attacks.

Administration of glyceryl trinitrate (GTN), a donor of nitric oxide, can induce migraine-like attacks in subjects with migraine. Provocation with GTN typically follows a biphasic pattern; it induces immediate headache in subjects with migraine, as well as in healthy controls, whereafter only subjects with migraine may develop a migraine-like headache several hours later. Interestingly, intravenous infusion with prostaglandin-E ₂ (PGE ₂ ) can also provoke a migraine-like headache, but seems to have a more rapid onset compared to GTN. The aim of the study was to shed light on the mechanistic aspect PGE ₂ has in migraine attack development. Therefore, PGE ₂ plasma levels were measured towards the (pre)ictal state of an attack, which we provoked with GTN. Blood samples from women with migraine (n = 37) and age-matched female controls (n = 25) were obtained before and ∼ 140 min and ∼ 320 min after GTN infusion. PGE ₂ levels were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Data was analyzed using a generalized linear mixed-effect model. Immediate headache after GTN infusion occurred in 85 % of migraine participants and in 75 % of controls. A delayed onset migraine-like attack was observed in 82 % of migraine subjects and in none of the controls. PGE ₂ levels were not different between the interictal and preictal state ( P  = 0.527) nor between interictal and ictal state (defined as having migraine-like headache) ( P  = 0.141). Hence, no evidence was found that a rise in PGE ₂ is an essential step in the initiation of GTN-induced migraine-like attacks.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 The Authors.)