Systemic Calcitonin Gene-Related Peptide (CGRP) modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities

Abstract

About 42% of people with migraine have a vestibular component causing balance problems and dizziness. In fact, VM is a major cause of vertigo in dizziness clinics and is estimated to affect 1% of the overall population. As migraine increases light, and sound sensitivities, it also increases sensitivities to movement or perceived movement in VM Patients with migraine, and especially VM, exhibit a heightened sense of sound, or phonophobia. Phonophobia is also related to hyperacusis (extreme sensitivity to sound). Behavioral evidence of hyperacusis and phonophobia in mice can be inferred using the acoustic startle reflex (ASR). The most common symptoms of VM were unsteadiness, balance disturbances, and light headedness. When balance disturbances were quantified, VM patients swayed more than migraine-only or healthy controls, when challenged with competing stimulus. In addition to static imbalance, VM patients also showed dynamic imbalances such as gait disturbances. In this study, we tested wildtype C57B6/J mice to determine if mice exhibited increased sound (measured by acoustic startle), static imbalance (measured by postural sway), and dynamic imbalance (measured by rotarod), when challenged with systemic CGRP (IP) 0.1 mg/kg. We found both sexes of mice were affected by systemic CGRP in sound and dynamic imbalance testing, yet only female mice showed increased postural sway after systemic CGRP, recapitulating the higher incidence of VM in females. These non-invasive assays of VM pave the way to further explore mechanisms of CGRP signaling in VM, and test effectiveness of migraine therapeutics in VM.