Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study.

Introduction: 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-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h 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.

Materials And Methods: We enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h 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 (T) and every 30 min until 180 min (T) after the start of the infusion.

Results: Blood samples were collected from patients with migraine ( = 19) and healthy individuals ( = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP ( = 0.027) at T (vs. T, adjusted value = 0.039) and T (vs. T, adjusted -value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks ( = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP ( = 0.205) or placebo ( = 0.428) days.

Discussion: 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.

Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03989817 and NCT04260035.