Abstract

Migraine is a common, disabling problem with three phases: premonitory, main headache attack, and postdrome. The headache phase is thought to involve activation of trigeminal neurons, whereas the premonitory and postdrome phases may involve dopaminergic mechanisms. In animal studies, dopamine has been found to cause vasodilation of cranial arteries at very low doses. Using intravital microscopy, we examined the effect of dopamine receptor agonists on dural blood vessel caliber and the effect of dopamine and specific dopamine receptor antagonists on trigeminovascular neurogenic dural vasodilation. Dopamine hydrochloride caused a significant vasoconstriction (P < 0.05) and increase in arterial blood pressure (P < 0.05) that was reversed by a α₂-adrenoceptor antagonist, yohimbine, rather than specific dopamine receptor antagonists. The D₁ receptor agonist caused a vasoconstriction (P < 0.05) and a blood pressure increase (P < 0.05), which was reversed by yohimbine and therefore α₂-adrenoceptor-mediated. None of the specific dopamine receptor antagonists were able to attenuate neurogenic dural vasodilation. Dopamine hydrochloride infusion (P < 0.05) and a D₁ receptor agonist were able to attenuate the vasodilation (P < 0.05), with maximal dilation returning after cessation of the dopamine agonist infusion. This response may be due to the vasoconstrictor effects of the α₂-adrenoceptor and an action at the D₁ receptor. In the intravital model of trigeminal activation, it seems that dopamine receptors do not play a major role and may not present an acute treatment option. Our data do not exclude a role for dopamine receptor modulators in short- or long-term prevention.