A Review of Calcitonin Gene-Related Peptide and Its Implications for Vestibular Disorders

Purpose of reviewCalcitonin gene-related peptide (CGRP) is an inflammatory neuropeptide widely present throughout the body and involved in many processes including vestibular function. This review reports recent advances in the understanding of CGRP, its role in vestibular physiology, current therapeutics targeting CGRP, and their possible role in vestibular disorders.Recent findingsCGRP modulates a diverse array of physiologic functions, including vasodilation, pain signaling, immunomodulation, wound healing, GI motility, and cochleovestibular function. CGRP plays a key role in the pathophysiology of migraine, which has led to the development of CGRP-blocking medications like small molecule receptor antagonists (gepants), and receptor or ligand monoclonal antibodies. Given the overlap of migraine and many vestibular conditions, CGRP-blocking medications have been used in a small number of studies targeting vestibular migraine with promising results, though with significant limitations in study design. Blocking CGRP may impact myriad functions and cause corresponding adverse effects clinically, though real-world evidence is still aggregating.SummaryInitial evidence of the role of CGRP in vestibular disorders is promising, though limited, and larger and more specific studies are needed to investigate signals toward efficacy. Due to the pan-presence of CGRP in the body, continued safety monitoring is underway and special attention should be paid to monitoring for side effects like the progression of hypertension, worsening of Raynaud's phenomenon, osteoporosis, impaired wound healing, autoimmune conditions, and vascular events. While CGRP's nuances and discrete role in cochleovestibular function continue to evolve, CGRP remains a compelling therapeutic target in the management of vestibular conditions.