Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties.
However, it remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute infusion of vasoactive intestinal polypeptide. A 2-hour infusion of vasoactive intestinal polypeptide caused migraine attacks, suggesting an important role of vasoactive intestinal polypeptide in migraine pathophysiology, reports a study.
The study is recently published in the JAMA Network.
Lanfranco Pellesi and colleagues from the Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark aimed to determine whether a 2-hour infusion of vasoactive intestinal polypeptide would provoke migraine attacks.
A randomized, double-blind, placebo-controlled, crossover study was conducted at the Danish Headache Center in Copenhagen, Denmark. Patients were eligible for inclusion if they were ages 18 to 40 years, weighed between 50 and 90 kg, had a diagnosis of migraine without aura as defined by the International Classification of Headache Disorders, and had a migraine frequency of 1 to 6 attacks per month.
Patients were randomly allocated to receive a 2-hour infusion of vasoactive intestinal polypeptide or placebo on 2 different days. The primary end point was the difference in incidence of experimentally induced migraine attacks during the observational period (0-12 hours) between vasoactive intestinal polypeptide and placebo.
The following findings were observed-
a.Twenty-one patients (17 [81%] women and 4 [19%] men; mean [range] age, 25.9 [19-40] years) were recruited in the study.
b.Fifteen patients (71%; 95% CI, 48%-89%) developed migraine attacks after vasoactive intestinal polypeptide compared with 1 patient (5%; 95% CI, 0%-24%) who developed a migraine attack after placebo (P < .001).
c.The VIP-induced migraine attacks mimicked patients' spontaneous attacks.
d.The area under the curve (AUC) of headache intensity scores (0-12 hours), as well as the AUC of the superficial temporal artery diameter (0-180 minute) were significantly greater after vasoactive intestinal polypeptide compared with placebo.
Therefore, it was concluded that a 2-hour infusion of vasoactive intestinal polypeptide caused migraine attacks, suggesting an important role of vasoactive intestinal polypeptide in migraine pathophysiology. Vasoactive intestinal polypeptide and its receptors could be potential targets for novel migraine drugs.
Pellesi L, Al-Karagholi MA, De Icco R, et al. Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(8):e2118543. doi:10.1001/jamanetworkopen.2021.18543