Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonism Reduces Motion Sickness Indicators in Mouse Models of Vestibular Migraine

Migraine and vestibular migraine (VM) are associated with enhanced motion sensitivity, and VM is the most common cause of spontaneous vertigo but remains poorly understood. It is now accepted that migraine involves the neuropeptide Calcitonin Gene-Related Peptide (CGRP); yet, it is not clear if CGRP signaling or it’s antagonism is involved in motion sensitivity of VM symptoms. Recent murine models of migraine used injections of CGRP or other migraine triggers (sodium nitroprusside (SNP) to induce migraine sensitivities, yet it is not known if these triggers can induce VM sensitivities. Moreover, it is not known if migraine blockers used in preclinical migraine models, can also block the motion-sensitivity of VM. To better understand CGRP’s role in VM motion sensitivity, we investigated two measures of motion sickness assessment (MSI scoring and motion-induced thermoregulation) after systemic injections of either CGRP or SNP in the wildtype C57B6/J mice, and found that MSI measures were confounded by CGRP’s effect on based on gastric distress, yet assessing motion sensitivity using thermoregulation was robust for both migraine triggers, and CGRP receptor antagonism by olcegepant, but not triptan treatments, rescued CGRP’s effect on increased motion sensitivity.