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

Structured Abstract Background Migraine and especially vestibular migraine are associated with enhanced motion sickness and motion-induced nausea. Murine models of migraine have used injections of Calcitonin Gene-Related Peptide (CGRP) or other migraine triggers [i.e., sodium nitroprusside (SNP)] to induce migraine sensitivities to touch and light. Yet, there is limited research on whether these triggers increase motion-induced nausea, and if migraine blockers can reduce these migraine symptoms. We hypothesized that systemic delivery of CGRP or SNP will increase motion sickness susceptibility and motion-induced nausea in mouse models, and that migraine blockers can block these changes induced by systemically delivered CGRP or SNP. Methods We investigated two measures of motion sickness assessment [motion sickness index (MSI) scoring and motion-induced thermoregulation] after intraperitoneal injections of either CGRP or SNP in C57B6/J mice. The drugs olcegepant, sumatriptan, and rizatriptan were used to assess the efficacy of migraine blockers. Results MSI measures were confounded by CGRP’s effect on gastric distress. However, analysis of tail vasodilations as a surrogate for motion-induced nausea was robust for both migraine triggers. Only olcegepant treatment rescued tail vasodilations. Conclusion These preclinical findings support the use of small molecule CGRP receptor antagonists for the treatment of motion-induced nausea of migraine, and show that triptan therapeutics are ineffective against motion-induced nausea of migraine.