Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine

In primates, histamine activates cerebral endothelial H1-receptors leading to formation of nitric oxide (NO). Twenty migraine patients received pretreatment with placebo or the histamine-H1-receptor antagonist, mepyramine, in a randomized, double blind fashion, followed in both groups by i.v. histamine (0.5 microgram kg-1 min-1 for 20 min). Headache characteristics were subsequently observed for 12 h. In patients given placebo histamine caused immediate headache during the infusion followed by a delayed migraine attack fulfilling IHS criteria for migraine without aura. The temporal profile of induced headache was exactly the same as after glyceryl trinitrate. Mepyramine pretreatment abolished both immediate headache and delayed migraine attacks. Our results suggest that a migraine attack can be caused by NO formation in the endothelium of cerebral arteries.