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Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial

IMPORTANCE: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only...

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Autores principales: Pellesi, Lanfranco, Al-Karagholi, Mohammad Al-Mahdi, De Icco, Roberto, Coskun, Hande, Elbahi, Fatima Azzahra, Lopez-Lopez, Cristina, Snellman, Josefin, Hannibal, Jens, Amin, Faisal Mohammad, Ashina, Messoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346940/
https://www.ncbi.nlm.nih.gov/pubmed/34357396
http://dx.doi.org/10.1001/jamanetworkopen.2021.18543
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author Pellesi, Lanfranco
Al-Karagholi, Mohammad Al-Mahdi
De Icco, Roberto
Coskun, Hande
Elbahi, Fatima Azzahra
Lopez-Lopez, Cristina
Snellman, Josefin
Hannibal, Jens
Amin, Faisal Mohammad
Ashina, Messoud
author_facet Pellesi, Lanfranco
Al-Karagholi, Mohammad Al-Mahdi
De Icco, Roberto
Coskun, Hande
Elbahi, Fatima Azzahra
Lopez-Lopez, Cristina
Snellman, Josefin
Hannibal, Jens
Amin, Faisal Mohammad
Ashina, Messoud
author_sort Pellesi, Lanfranco
collection PubMed
description IMPORTANCE: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute infusion of VIP. OBJECTIVE: To determine whether a 2-hour infusion of VIP would provoke migraine attacks. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled, crossover study was conducted between May and September 2020 at the Danish Headache Center in Copenhagen, Denmark. Patients were eligible for inclusion if they were ages 18 to 40 years, weighed between 50 and 90 kg, had a diagnosis of migraine without aura as defined by the International Classification of Headache Disorders, and had a migraine frequency of 1 to 6 attacks per month. INTERVENTIONS: Patients were randomly allocated to receive a 2-hour infusion of VIP or placebo on 2 different days. MAIN OUTCOMES AND MEASURES: The primary end point was the difference in incidence of experimentally induced migraine attacks during the observational period (0-12 hours) between VIP and placebo. RESULTS: Twenty-one patients (17 [81%] women and 4 [19%] men; mean [range] age, 25.9 [19-40] years) were recruited in the study. Fifteen patients (71%; 95% CI, 48%-89%) developed migraine attacks after VIP compared with 1 patient (5%; 95% CI, 0%-24%) who developed a migraine attack after placebo (P < .001). The VIP-induced migraine attacks mimicked patients’ spontaneous attacks. The area under the curve (AUC) of headache intensity scores (0-12 hours), as well as the AUC of the superficial temporal artery diameter (0-180 minute) were significantly greater after VIP compared with placebo (AUC(0-12h), P = .003; AUC(0-180min), P < .001). CONCLUSIONS AND RELEVANCE: A 2-hour infusion of VIP caused migraine attacks, suggesting an important role of VIP in migraine pathophysiology. VIP and its receptors could be potential targets for novel migraine drugs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04260035
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spelling pubmed-83469402021-08-20 Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial Pellesi, Lanfranco Al-Karagholi, Mohammad Al-Mahdi De Icco, Roberto Coskun, Hande Elbahi, Fatima Azzahra Lopez-Lopez, Cristina Snellman, Josefin Hannibal, Jens Amin, Faisal Mohammad Ashina, Messoud JAMA Netw Open Original Investigation IMPORTANCE: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute infusion of VIP. OBJECTIVE: To determine whether a 2-hour infusion of VIP would provoke migraine attacks. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled, crossover study was conducted between May and September 2020 at the Danish Headache Center in Copenhagen, Denmark. Patients were eligible for inclusion if they were ages 18 to 40 years, weighed between 50 and 90 kg, had a diagnosis of migraine without aura as defined by the International Classification of Headache Disorders, and had a migraine frequency of 1 to 6 attacks per month. INTERVENTIONS: Patients were randomly allocated to receive a 2-hour infusion of VIP or placebo on 2 different days. MAIN OUTCOMES AND MEASURES: The primary end point was the difference in incidence of experimentally induced migraine attacks during the observational period (0-12 hours) between VIP and placebo. RESULTS: Twenty-one patients (17 [81%] women and 4 [19%] men; mean [range] age, 25.9 [19-40] years) were recruited in the study. Fifteen patients (71%; 95% CI, 48%-89%) developed migraine attacks after VIP compared with 1 patient (5%; 95% CI, 0%-24%) who developed a migraine attack after placebo (P < .001). The VIP-induced migraine attacks mimicked patients’ spontaneous attacks. The area under the curve (AUC) of headache intensity scores (0-12 hours), as well as the AUC of the superficial temporal artery diameter (0-180 minute) were significantly greater after VIP compared with placebo (AUC(0-12h), P = .003; AUC(0-180min), P < .001). CONCLUSIONS AND RELEVANCE: A 2-hour infusion of VIP caused migraine attacks, suggesting an important role of VIP in migraine pathophysiology. VIP and its receptors could be potential targets for novel migraine drugs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04260035 American Medical Association 2021-08-06 /pmc/articles/PMC8346940/ /pubmed/34357396 http://dx.doi.org/10.1001/jamanetworkopen.2021.18543 Text en Copyright 2021 Pellesi L et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Pellesi, Lanfranco
Al-Karagholi, Mohammad Al-Mahdi
De Icco, Roberto
Coskun, Hande
Elbahi, Fatima Azzahra
Lopez-Lopez, Cristina
Snellman, Josefin
Hannibal, Jens
Amin, Faisal Mohammad
Ashina, Messoud
Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title_full Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title_fullStr Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title_full_unstemmed Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title_short Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
title_sort effect of vasoactive intestinal polypeptide on development of migraine headaches: a randomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346940/
https://www.ncbi.nlm.nih.gov/pubmed/34357396
http://dx.doi.org/10.1001/jamanetworkopen.2021.18543
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