Potential neurogenic and vascular roles of nitric oxide in migraine headache and aura

It has long been known that nitrate and nitrite medications consistently ca use significant headache as a side effect. Classical research has shown tha t cerebral vasodilation accompanies the use of these medications. Merit mod ern studies suggest that these vasodilators exert their action on blood ves sels via nitric oxide and its second messenger, cyclic guanosine monophosph ate. This paper reviews research studies and theoretical articles which add ress the concept that nitric oxide plays a major role in the vasodilation a ssociated with the headache phase of migraine with aura. A brief discussion of nitric oxide biochemistry and pharmacology follows. In addition, there is a review of evidence examining the possible contribut ions of nitric oxide to the neurogenic and vascular events associated with spreading cortical depression, an animal model of migraine aura. The parado xical hypotheses that nitric oxide may contribute to both the propagation o f spreading cortical depression and its limitation are presented. Finally, a rationale for the experimental use of nitric oxide agonists and antagonis ts in the abortion of migraine aura is introduced.