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Glyceryl trinitrate induced headache in migraineurs – relation to attack frequency

Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate headache in healthy subjects, whilst migraineurs develop a more severe headache, resembling spontaneous migraine attacks. In order to investigate whether this increased nitric oxide sensitivity depends upon the frequency of spontaneously occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5 µg/kg/min) was given to 15 migraine patients with rare attacks (≤4 attacks/year) of migraine without aura. Fourteen age‐matched migraine patients with frequent attacks of migraine without aura (≥12 attacks/year) and 14 healthy subjects served as controls. No significant difference between the migraine groups for any of several parameters was detected, although the trend was always towards more headaches in frequent migraineurs. Both migraineurs with frequent and rare attacks experienced a headache that was significantly more severe, longer lasting, and fulfilled the diagnostic criteria for migraine without aura more often, compared to the healthy subjects (P = 0.0001). Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be related to a basic – probably genetically determined – pathophysiological mechanism involving nitric oxide, and not to the environmental influences, which to a large extent determine the expression of migraine.