Received for publication January 4, 2005.
Revised March 16, 2005.
Accepted for publication March 16, 2005.

The role of dopamine in a model of trigeminovascular nociception

Abstract

Migraine is a common disabling problem with three phases, premonitory, main headache attack and postdrome. The headache phase is believed to involve activation of trigeminal neurons, while the premonitory and postdrome phases may involve dopaminergic mechanisms. In animal studies, at very low doses dopamine has been found to cause vasodilation of cranial arteries. Using intravital microscopy we examined the effect of dopamine receptor agonists on dural blood vessel calibre, 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 ₂-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 ₂-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), maximal dilation returning after cessation of the dopamine agonist infusion. This response may be due to the vasoconstrictor effects of the ₂-adrenoceptor and an action at the D₁ receptor. In the intravital model of trigeminal activation it appears 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.

Key words: dopamine, headache, intravital microscopy, migraine, neurogenic vasodilation, trigeminal