2022 MSC Poster Contest Presentation: Calcitonin Gene-Related Peptide (CGRP) and Motion Sensitivity: Implications for Vestibular Migraine

Title: Calcitonin gene-related peptide (CGRP) and motion sensitivity: Implications for vestibular migraine

Presenter: Shafaqat Rahman, PhD student, University of Rochester, US

Methodology, findings and conclusions of the research
Migraine is a neurological disorder characterized not simply by a recurrent headache, but also by enhanced sensitivity to natural stimuli like light and sound. Patients with vestibular migraine have a history of migraine but may also exhibit an enhanced motion sensitivity that leads to recurrent vertigo and dizziness. My thesis explores CGRP’s effects on motion sensitivity in mice, by looking at thermoregulatory responses to provocative motion (as a surrogate for nausea) and center of pressure (CoP) measurements (as a surrogate for postural sway).

We’ve learned that CGRP does impair thermoregulatory responses to provocative motion and that we can recapitulate a healthy response to motion with the use of a CGRP blocker (olcegepant) but not with triptans. We’ve also learned that CGRP increases CoP measurements in female but not male mice. These increased CoP values in females due to CGRP resembles clinical understanding that vestibular migraine and chronic pain disorders affect more women than men, and also suggests an enhanced CGRP role in these symptoms related to female physiology. We’re currently exploring the effects of CGRP in novel mouse strains with enhanced CGRP signaling (in nestin-hRAMP1 mice, where the hRAMP1 subunit is upregulated) as well as impaired CGRP signaling (nestin-RCPnull, where the RCP protein is deleted), to better understand the role of CGRP signaling in these symptoms.

Implications of the research for understanding migraine and/or its comorbidities
The implications of this research are significant, as vestibular migraine is still in a nascent phase of clinical understanding but is a prevalent problem among women in their 30-40s. There is a need to understand symptoms related to this disorder in preclinical mouse models, in order to develop more tailored therapeutic strategies. We feel confident in our thermoregulatory assay as a correlate for nausea, because we know in the dizziness clinic that triptans (e.g., sumatriptan/rizatriptan) do not have an ameliorative effect on nausea, and this lack of therapeutic effect mirrors our preclinical results. In addition, there are no solid preclinical models for assessing nausea in rodents, because mice do not have an emesis reflex and cannot vocalize their nausea. As such, measuring thermoregulation provides a unique alternative to assessing nausea in mice, which we recommend other scientists to consider when looking at a similar symptom in their research endeavors. Our observations for increased CoP values in females due to CGRP does highlight a sex-specific preponderance of this neuropeptide, which may be dysregulating key components of vestibular, proprioceptive, and motor control. We believe that this sway should be further explored with CGRP blockers and in novel strains that modulate key aspects of CGRP signaling and are currently doing so in our novel mouse strains.