TY - JOUR

T1 - Calcitonin gene-related peptide causes migraine aura

AU - Al-Khazali, Haidar M.

AU - Ashina, Håkan

AU - Wiggers, Astrid

AU - Rose, Kathrine

AU - Iljazi, Afrim

AU - Christensen, Rune Häckert

AU - Schytz, Henrik Winther

AU - Amin, Faisal Mohammad

AU - Ashina, Messoud

N1 - Publisher Copyright: © 2023, Springer-Verlag Italia S.r.l., part of Springer Nature.

PY - 2023

Y1 - 2023

N2 - Background: Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often precedes the headache, remains largely unexplored. This study aims to instigate CGRP’s potential in triggering aura, thus establishing its role in the early stages of migraine. Methods: In this open-label, non-randomized, single-arm trial, 34 participants with migraine with aura received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min on a single experimental day. Participants were required to be free of headache and report no use of acute medications 24 h before infusion start. The primary endpoint was the incidence of migraine aura during the 12-hour observational period after the start of infusion. Results: Thirteen (38%) of 34 participants developed migraine aura after CGRP infusion. In addition, 24 (71%) of 34 participants developed migraine headache following CGRP infusion. Conclusions: Our findings suggest that CGRP could play an important role in the early phases of a migraine attack, including during the aura phase. These insights offer a new perspective on the pathogenesis of migraines with aura. They underscore the need for additional research to further explore the role of CGRP in these initial stages of a migraine attack, and potentially inform future development of therapeutic interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04592952. Graphical Abstract: [Figure not available: see fulltext.]

AB - Background: Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often precedes the headache, remains largely unexplored. This study aims to instigate CGRP’s potential in triggering aura, thus establishing its role in the early stages of migraine. Methods: In this open-label, non-randomized, single-arm trial, 34 participants with migraine with aura received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min on a single experimental day. Participants were required to be free of headache and report no use of acute medications 24 h before infusion start. The primary endpoint was the incidence of migraine aura during the 12-hour observational period after the start of infusion. Results: Thirteen (38%) of 34 participants developed migraine aura after CGRP infusion. In addition, 24 (71%) of 34 participants developed migraine headache following CGRP infusion. Conclusions: Our findings suggest that CGRP could play an important role in the early phases of a migraine attack, including during the aura phase. These insights offer a new perspective on the pathogenesis of migraines with aura. They underscore the need for additional research to further explore the role of CGRP in these initial stages of a migraine attack, and potentially inform future development of therapeutic interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04592952. Graphical Abstract: [Figure not available: see fulltext.]

KW - Cortical spreading depolarization

KW - Headache disorders

KW - Pathophysiology

KW - Trigeminovascular System

U2 - 10.1186/s10194-023-01656-4

DO - 10.1186/s10194-023-01656-4

M3 - Journal article

C2 - 37679723

AN - SCOPUS:85170161353

VL - 24

JO - Journal of Headache and Pain

JF - Journal of Headache and Pain

SN - 1129-2369

IS - 1

M1 - 124

ER -