Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.