Calcitonin gene‐related peptide in the audiovestibular system

OBJECTIVE: This study aimed to summarize and analyze the current literature related to calcitonin gene-related peptide (CGRP), the vestibular system, and vestibular migraine. BACKGROUND: CGRP is a neuropeptide that has been implicated in the pathophysiology of migraine. Vestibular migraine (VM) is a subtype of migraine that causes recurring episodes of vestibular symptoms like vertigo and is often associated with migrainous symptoms. Although the pathophysiology of VM is not completely understood, CGRP expression in the central and peripheral vestibular systems has suggested that it may also play a role in this closely related disease. METHODS: We performed a synthesis of current literature regarding the neuroanatomy of CGRP and the vestibular system and how CGRP stimulation and blockade affect vestibular function. Data was included from human and animal experiments indexed on PubMed. RESULTS: CGRP expression in rodents was found in the vestibular cerebellum, vestibular nuclei, and in lateral olivocochlear efferent neurons. αCGRP-null (-/-) mice have a decreased gain of the vestibular-ocular reflex as well as impaired balance testing. CGRP infusion in rodents causes phonophobia, motion sickness, and imbalance. In vasodilator-induced migraine models, CGRP expression was increased in central vestibular structures, with associated vestibular dysfunction and motion sensitivity. In humans, monoclonal antibodies targeting the CGRP pathway can reduce dizziness from vestibular migraine. CONCLUSION: CGRP is expressed in the central and peripheral audiovestibular system and is implicated in the pathophysiology of VM. Preliminary results have shown promise for the treatment of VM with CGRP-targeted therapies although more high-level placebo-controlled data is needed especially for orally administered gepants. Further study is required to better understand how CGRP influences vestibular function and its role in vestibular migraine.