1. Among patients with migraine without aura, 2-hour infusion of vasoactive intestinal polypeptide (VIP) initiated migraine attacks in 71% of participants compared to 5% after placebo infusion.
2. VIP infusion resulted in significantly greater dilation of the superficial temporal artery compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The release of vasoactive intestinal polypeptide (VIP) may be involved in provoking migraines through downstream signalling pathways on cranial vessels. This randomized controlled, crossover study investigated whether VIP infusion for two hours can initiate migraine attacks. Participants were included if they had previously been diagnosed with migraines without aura. They were recruited from the Danish Headache Centre between May 2020 and September 2020. Twenty-one participants were randomized to receive an intervention of VIP or placebo over two hours; two weeks following the first intervention, the participants received the intervention they had not received the first time. The primary outcome was the difference in the incidence of migraine attacks within 12 hours of intervention between VIP and placebo. Out of 21 participants, 15 had a migraine attack after VIP compared to 1 who had a migraine post-placebo infusion (15/21; 71% [95% CI: 48-89] vs. 1/21; 5% [95% CI: 0-24]; p< 0.001). The median time to migraine attack onset was 1 hour 40 minutes (IQR: 1 hour-1 hour 50 minutes), and the median headache intensity was 3/10 (IQR: 2-5). Nausea and photophobia were more commonly reported after VIP compared to placebo. In the hospital after infusion, superficial temporal artery (STA) diameter was recorded to assess vasodilation; STA diameter was significantly greater after VIP infusion compared to placebo (p< 0.001). When comparing this study to a previous study of VIP infusion in healthy volunteers, adverse events (flushing, warm sensation, heart palpitations) were similar between patients with migraines and healthy volunteers; however, migraine attacks and associated symptoms (nausea, photophobia, phonophobia) were more common among patients with previous migraines. Overall, VIP infusion for 2 hours induced migraine attacks and resulted in prolonged STA dilation in migraine patients without aura. This study was limited, however, by its generalizability as the sample size was small (21 participants), participants were recruited from one centre, and only those with migraine without aura were included.
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