Source of pain and primitive dysfunction in migraine: an identical site?

Abstract

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,...

Intravenous Endothelin‐1 Infusion Does Not Induce Aura or Headache in Migraine Patients With Aura

“…Since there is a substantial pulmonary clearance of ET‐1, with a mean first‐pass clearance of approximately 50%, an explanation for this could be that a higher concentration of intravascular ET‐1 would reach the cerebral circulation in patients with a PFO. Another, more likely, explanation is based on the observation that microemboli, for example, in the form of air bubbles, entering the cerebral circulation can induce CSD in animals and that intravenous administration of agitated saline in migraine patients with PFO may occasionally induce migraine aura . Further, rare occurrences of suspected transient ischemic attacks and neuroimaging‐verified ischemic stroke following sclerotherapy have been reported almost exclusively in patients with right‐to‐left cardiac shunts, mostly PFOs .…”

“…A robust method for experimental provocation of migraine aura, however, has not yet been established . Migraine provocation using vasodilating drugs (glyceryl trinitrate, calcitonin‐gene related peptide, and cilostazol) has been attempted in patients suffering from migraine with aura specifically . Interestingly, in these studies, the drugs generally induced migraine attacks without aura, even in patients who previously experienced attacks with aura exclusively, while migraine attacks with aura were only rarely triggered.…”

The Frontotemporal Region Plays a Role in the Genesis of Migraine Without Aura

“…3 In the same patients, early onset migraine did not occur with nitroglycerin applied to the wrist, or to the asymptomatic temple in cases of unilateral migraine. In particular, studies by Wolff 1 led to the concept, which is still debated, that vasodilatation of the branches of the external carotid artery (middle meningeal artery and arteries of the scalp) is correlated with migraine pain.…”

Induction of a Migraine Aura in a Patient Suffering From Migraine Without Aura

“…In patients suffering from migraine with aura (MWA) or migraine without aura (MWOA), a migraine attack can be triggered by nitroglycerin (NTG) 1‐3 . The number and the latency of successful inductions by NTG vary according to its route of administration: sublingual, 4 intravenous, 2 and transdermal 5 . Our study group demonstrated that topical NTG administration at the typical site of pain is a highly successful, rapid, and tolerated method of migraine induction 5,6 .…”