The role of dopamine in a model of trigeminovascular nociception.
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 alpha2-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 alpha2-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 alpha2-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.
Akerman
S
S
Institute of Neurology, Queen Square, London, WC1N 3BG UK.
Goadsby
P J
PJ
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D014276:Trigeminal Nerve / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; C493601:Drd4 protein, rat; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D004298:Dopamine