Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: A transcranial Doppler study

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.