Vascular responses to molecular migraine triggers: a systematic review of magnetic resonance angiography studies

To synthesize and interpret magnetic resonance angiography (MRA) findings on vascular changes after administration of established molecular migraine triggers in adults with migraine and in healthy individuals, focusing on the middle meningeal artery (MMA) and middle cerebral artery (MCA). A systematic review of experimental studies using MRA to assess extracerebral and intracerebral arterial responses to established molecular migraine triggers was conducted. Eligible studies included adults with migraine or healthy volunteers, use of MRA, and oral ingestion or intravenous infusion of an established molecular migraine trigger. Studies not meeting these criteria, as well as conference abstracts, preprints, reviews, case reports, and case series, were excluded. Sixteen eligible MRA studies were identified. The triggers used included calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), vasoactive intestinal polypeptide, nitroglycerin, cilostazol, sildenafil, and levcromakalim. All triggers induced extracerebral (meningeal) arterial dilation, often accompanied by headache or migraine attacks. Dilation induced by neuropeptides was confined to extracerebral arteries, consistent with limited blood-brain barrier penetration. In contrast, nitroglycerin and levcromakalim also dilated cerebral arteries. Across all studies, sumatriptan consistently reversed extracerebral arterial dilation and alleviated migraine pain. Established molecular triggers reliably induce extracerebral arterial dilation, an effect reversed by sumatriptan. These findings support the hypothesis that sustained meningeal vasodilation might contribute causally to migraine pathogenesis. Standardized MRA protocols, rigorous methodological designs, and well-controlled studies are needed to further refine our understanding of these vascular mechanisms and to guide the development of more targeted therapies for migraine.