The Influence of Calcitonin Gene-Related Peptide on Cerebral Hemodynamics in Nonmigraine Subjects with Calcitonin Gene-Related Peptide-Induced Headaches

BACKGROUND: Calcitonin gene-related peptide (CGRP) is regarded as an important molecule in trigeminovascular sensitization (TVS). CGRP-induced headaches (CGRP-IH) are evoked by intravascular administration of CGRP in nonmigraine and migraine subjects. CGRP might be associated with vasodilatation of the middle cerebral artery (MCA). It is unclear whether CGRP-induced hemodynamic changes relate to CGRP-IH in nonmigraine subjects. METHODS: Twenty healthy subjects participated in our study. Polymodal recording of mean arterial velocity in MCA (vm MCA), end-tidal carbon dioxide partial pressure (Et-CO(2)), mean arterial pressure (MAP), and heart rate (HR) was employed using transcranial Doppler (TCD) sonography. During the experiment, we administered intravenous infusion of CGRP at a rate of 1.5 mcg/min. The vm MCA, Et-CO(2), HR, and MAP were determined at time points T(0), T(1), T(2), and T(3). We calculated the responses at different time points and combined them into a single response vm MCA(tot), Et-CO(2tot), HR(tot), and MAP(tot). RESULTS: We found significant differences along the time points in vm MCA (p = <0.001), Et-CO(2) (p = 0.003), MAP (p < 0.001), and HR (p < 0.001). The relationship between vm MCA(tot) and Et-CO(2tot) was significant and positive (p = 0.005). The t-test showed significant differences between CGRP-IH and non-CGRP-IH subjects in vm MCA(tot) (p = 0.021) but not in Et-CO(2tot) (p = 0.838), MAP(tot) (p = 0.839), and HR(tot) (p = 0.198). Only vm MCA(tot) showed a significant relationship with CGRP-IH (p = 0.028). CONCLUSIONS: Our study provides evidence for vasodilatation of MCA in relation to CGRP-IH due to intravascular CGRP detected by multimodal TCD. In the context of TVS induced by CGRP, MCA vasodilatation seems to represent an epiphenomenon of the underlying TVS.