AUTHOR=Pellesi Lanfranco , Al-Karagholi Mohammad Al-Mahdi , De Icco Roberto , Chaudhry Basit Ali , Lopez Cristina Lopez , Snellman Josefin , Hannibal Jens , Amin Faisal Mohammad , Ashina Messoud TITLE=Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study JOURNAL=Frontiers in Neurology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.871176 DOI=10.3389/fneur.2022.871176 ISSN=1664-2295 ABSTRACT=Background: The activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-hour infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-hour infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks. Methods: We enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-hour infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min, until 180 min (T180) after the start of the infusion. Results: Blood samples were collected from migraine patients (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p value = 0.039) and T60 (vs. T180, adjusted p value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days. Conclusion: Plasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine.