The vascular role of CGRP: a systematic review of human studies

Intravenous infusion of human alpha calcitonin gene-related peptide (h-& alpha;-CGRP) has been applied to explore migraine pathogenesis and cerebral hemodynamics during the past three decades. Cumulative data implicate h-& alpha;-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-& alpha;-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 V-MCA), and diameter of superficial temporal artery (STA). Upon the start of h-& alpha;-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 V-MCA 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-& alpha;-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.

Automated summary

Intravenous infusion of h-α-CGRP has been used to investigate migraine pathogenesis and cerebral hemodynamics for the last 30 years. Studies have shown that h-α-CGRP regulates vascular tone. By analyzing clinical studies, this systematic review found that h-α-CGRP infusion caused flushing, palpitation, warm sensation, changes in heart rate, blood pressure, blood flow velocity, and artery diameter. These vascular changes lasted from 20 to >120 minutes without any serious adverse events. The involvement of CGRP in systemic hemodynamics raises concerns about long-term CGRP blockade in migraine patients with and without cardiovascular complications.