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

Abstract

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-CO2), 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-CO2, 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 MCAtot, Et-CO2tot, HRtot, and MAPtot. Results. We found significant differences along the time points in vm MCA ( $p=<0.001$ ), Et-CO2 ( $p=0.003$ ), MAP ( $p<0.001$ ), and HR ( $p<0.001$ ). The relationship between vm MCAtot and Et-CO2tot was significant and positive ( $p=0.005$ ). The $t$ -test showed significant differences between CGRP-IH and non-CGRP-IH subjects in vm MCAtot ( $p=0.021$ ) but not in Et-CO2tot ( $p=0.838$ ), MAPtot ( $p=0.839$ ), and HRtot ( $p=0.198$ ). Only vm MCAtot 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.