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

Lanfranco Pellesi, Mohammad Al Mahdi Al-Karagholi, Roberto De Icco, Basit Ali Chaudhry, Cristina Lopez Lopez, Josefin Snellman, Jens Hannibal, Faisal Mohammad Amin, Messoud Ashina*

*Corresponding author for this work

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Abstract

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 (T0) and every 30 min until 180 min (T180) after the start of the infusion. Results: Blood samples were collected from patients with migraine (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. 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.

Original languageEnglish
Article number871176
JournalFrontiers in Neurology
Volume13
Number of pages7
ISSN1664-2295
DOIs
Publication statusPublished - 1 Apr 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Pellesi, Al-Karagholi, De Icco, Chaudhry, Lopez, Snellman, Hannibal, Amin and Ashina.

Keywords

  • autonomic
  • headache
  • PACAP38
  • pain
  • parasympathetic system

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