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Updated: Jul 22, 2025
Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
The vascular role of CGRP: a systematic review of human studies
Mohammad Al-Mahdi Al-Karagholi1, Veberka Kalatharan1, Peter Schunck Fagerberg1
1Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Insights
Intravenous infusion of human alpha calcitonin gene-related peptide (h-α-CGRP) causes vasodilation and affects heart rate and blood pressure. This suggests CGRP
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Pharmacology
Background:
- Human alpha calcitonin gene-related peptide (h-α-CGRP) is implicated in migraine pathogenesis.
- h-α-CGRP plays a role in regulating vascular tone.
Purpose of the Study:
- To systematically review clinical studies on vascular changes induced by intravenous h-α-CGRP infusion in humans.
- To assess the hemodynamic effects of h-α-CGRP.
Main Methods:
- Systematic review of PubMed and EMBASE databases.
- Included 11 studies with 61 healthy and 177 migraine participants.
- Analyzed reported hemodynamic effects like flushing, heart rate, blood pressure, cerebral blood flow velocity, and artery diameter.
Main Results:
- Intravenous h-α-CGRP infusion caused universal vasodilation.
- Common effects included flushing (99%) and warm sensation (97%).
- Heart rate increased (14%-58%), mean arterial blood pressure decreased (7%-12%), middle cerebral artery blood flow velocity decreased (9.5%-21%), and superficial temporal artery diameter increased (41%-43%).
Conclusions:
- Intravenous h-α-CGRP induces significant systemic hemodynamic changes, primarily vasodilation.
- While generally safe in short-term infusion, these effects raise concerns for long-term CGRP blockade in migraine management, especially in patients with cardiovascular conditions.
Abstract:
Intravenous infusion of human alpha calcitonin gene-related peptide (h-α-CGRP) has been applied to explore migraine pathogenesis and cerebral hemodynamics during the past three decades. Cumulative data implicate h-α-CGRP in regulating the vascular tone. In this systematic review, we searched PubMed and EMBASE for clinical studies investigating the vascular changes upon intravenous infusion of h-α-CGRP in humans. A total of 386 studies were screened by title and abstract. Of these, 11 studies with 61 healthy participants and 177 participants diagnosed with migraine were included. Several studies reported hemodynamic effects including flushing, palpitation, warm sensation, heart rate (HR), mean arterial blood pressure (MABP), mean blood flow velocity of middle cerebral artery (mean VMCA), and diameter of superficial temporal artery (STA). Upon the start of h-α-CGRP infusion, 163 of 165 (99%) participants had flushing, 98 of 155 (63%) participants reported palpitation, and 160 of 165 (97%) participants reported warm sensation. HR increased with 14%-58% and MABP decreased with 7%-12%. The mean VMCA was decreased with 9.5%-21%, and the diameter of the STA was dilated with 41%-43%. The vascular changes lasted from 20 to >120 min. Intravenous infusion of h-α-CGRP caused a universal vasodilation without any serious adverse events. The involvement of CGRP in the systemic hemodynamic raises concerns regarding long-term blockade of CGRP in migraine patients with and without cardiovascular complications.
