# CGRP's effect on hearing and balance in a mouse model of migraine

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $326,988

## Abstract

Migraine is a severe and chronic neurological disorder that affects ~18% of people worldwide, majority
female (3:1). Migraine is characterized by recurrent attacks of debilitating headaches and nausea, with
heightened sensory sensitivities, such as light (photophobia) and sound (phonophobia). Recently it has
become recognized that ~42% of migraine patients also suffer from balance problems and dizziness, termed
vestibular migraine (VM). VM is a major cause of vertigo in dizziness clinics, and is estimated to affect 1% of
the overall population. Clinically, triptans (serotonin 5-HT 1B/1D receptor agonists) can reduce photophobia
and headaches in migraine, but often do not relieve other VM symptoms. Thus, there is an urgent need for
validated preclinical models for VM.
 The neuropeptide calcitonin gene-related peptide (CGRP) is recognized as a key player in migraine based
on the efficacy of CGRP blockers in clinical trials against headache, and injection of CGRP triggers migraine.
We have developed CGRP-sensitized transgenic mouse models for migraine that have heightened responses
to light (photophobia) when CGRP is delivered either centrally or systemically. We have shown that CGRP
blockers can block CGRP-induced photosensitivity in these mice, yet CGRP blockers delivered systemically
cannot effectively penetrate the CNS, and these blockers are not effective against centrally-induced
photophobia, suggesting that photosensitivity in migraine involves both systemic and central components.
CGRP is also widely distributed throughout the vestibular CNS, and CGRP-containing efferent fibers project to
all inner ear endorgans. CGRP is also signaling in the vestibular and auditory systems, as we discovered in a
different mouse model, that the loss of CGRP reduces the vestibulo-ocular reflex (VOR) gain, reduces otolith-
evoked dynamics reduces, reduces sound-evoked activity in the cochlear nerve, and impairs rotarod (balance)
performance. Yet, it is not yet known if CGRP is acting centrally or peripherally in VM; which would influence
treatment routes and efficacy. We propose to measure mouse homologues of clinical VM symptoms namely;
phonophobia, imbalance, nausea, and motion-sickness susceptibility; and will investigate these measures in
three mouse lines: i) wildtype (WT) littermate controls and CGRP-sensitized mouse models with ii) neuronally-
sensitized CGRP receptors (nestinRAMP1) or iii) globally-sensitized CGRP receptors (global RAMP1). Our
hypothesis is that elevated CGRP-sensitivity will contribute to increased sensitivities found in VM; and
that these VM symptoms will be ameliorated by CGRP blockers.
 Information gained from these studies will provide a direct assessment of whether CGRP-sensitized mouse
models that have been shown to mirror the photophobia of migraine, can also mirror deficits observed in VM.
Such a preclinical model of VM could be used for future translational studies to develop and test new
therapeutics. !

## Key facts

- **NIH application ID:** 9931049
- **Project number:** 5R01DC017261-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** ANNE E LUEBKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,988
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931049

## Citation

> US National Institutes of Health, RePORTER application 9931049, CGRP's effect on hearing and balance in a mouse model of migraine (5R01DC017261-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9931049. Licensed CC0.

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