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=13

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=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Materials and Methods</title><p>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<sub>0</sub>) and every 30 min until 180 min (T<sub>180</sub>) after the start of the infusion.</p></sec><sec><title>Results</title><p>Blood samples were collected from patients with migraine (<italic>n</italic> = 19) and healthy individuals (<italic>n</italic> = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (<italic>p</italic> = 0.027) at T<sub>30</sub> (vs. T<sub>180</sub>, adjusted <italic>p-</italic>value = 0.039) and T<sub>60</sub> (vs. T<sub>180</sub>, adjusted <italic>p</italic>-value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (<italic>p</italic> = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (<italic>p</italic> = 0.205) or placebo (<italic>p</italic> = 0.428) days.</p></sec><sec><title>Discussion</title><p>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.</p></sec><sec><title>Clinical Trial Registration</title><p><ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, identifier: NCT03989817 and NCT04260035.</p></sec>