SUMMARY Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is ofcrucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.Headache is a well known side effect of nitrates which are present in some foods and pharmaceutical preparations. Nitroglycerin or isosorbide dinitrate is commonly administered by the sublingual route to migraine patients as a simple method of inducing a migraine attack.'2 They generally produce a typical throbbing headache, with nausea and photophobia, indistinguishable from a spontaneous migraine crisis. In such cases headache often begins many hours after the drug is administered3 and thus cannot be caused by nitrate induced vasodilatation, in view of nitroglycerin's extremely short half-life and the relatively brief effectiveness of the isosorbide dinitrate metabolites.45 In the first few minutes after sublingual administration, however, patients often complain of short lasting and sometimes painful pulsations which spontaneously disappear within about half an hour.Pharmacokinetic studies of nitroglycerin in humans have demonstrated an arteriovenous gradient during intravenous infusion of the drug, due to an avid uptake by venous blood vessels.6 Moreover, studies on transdermal nitroglycerin systems have shown marked differences in nitroglycerin plasma concentrations according to the site of blood collection; the concentration is higher in plasma obtained near the administration site than in other body areas.7 This Correspondence to: Salvatore Bonuso, Clinica Neurologica, I1 Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli, Via S Pansini 5, 80131 Napoli, Italy. Accepted 5 July 1989 implies that the site of nitroglycerin application greatly influences the drug's bioavailability.The aims of our study were to show that: 1) nitroglycerin ointment applied to a typical migraine site is able to induce an early onset attack and that 2) the induced migraine attack is triggered from the stimulation of the typical migraine site.Nitroglycerin ointment applied to the head at the frontotemporal region allowed, for the first time, some observations which were not previously possible using common inductive methods. Patients and methodsFifty-three subjects (17 male, 36 female, mean age 33, SD 8, range 20-45 years) suffering from migraine (50 common, three classic), diagnosed according to the "ad hoc committee" criteria,...
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