# The role of TRPM8 and artemin in migraine

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $247,500

## Abstract

Migraine is one of the most debilitating disorders in humans, affecting greater than 15% of the population
with minimal therapeutic avenues for migraine sufferers. The challenge in treatment is that migraine
involves many sensory pathways, including irregular excitability in central and peripheral nociceptive
neurons. To address this complex disorder, several groups have recently performed genome-wide
associated studies (GWAS) to ascertain candidate molecules mediating migraine pathology, identifying the
cold and menthol receptor TRPM8 as a migraine susceptibility gene. Interestingly, these studies identified
mutations only in noncoding regions of TRPM8, therefore making it likely that these mutations alter
expression levels and not channel function. While it is not known what role, if any, the channel has in
migraine, TRPM8 serves an important role in pathological cold pain, suggesting there may be a corollary
between cold and migraine pain. Recently, we found that the glial cell line-derived neurotrophic factor
(GDNF) family ligand artemin and its receptor, GDNF family receptor alpha 3 (GFRa3), are the principle
mediators of TRPM8-dependent cold pain, of note as each has also been linked to migraine. These results
have led us to the hypothesis that TRPM8 channels and afferents, via altered signaling due to artemin
interacting with GFRa3, are a component of the underlying mechanisms of migraine. To test this, we
propose to use this exploratory mechanism to (1) determine if TRPM8 channels or neurons are involved in
migraine-like pain behaviors in mice, then (2) similarly ask if artemin and GFRa3 are required for migraine
pathogenesis. At the completion of this exploratory study, we will have determined if either TRPM8 or
artemin/GFRa3 signaling serve a role in migraine. Moreover, the proposed experiments will determine if
either of the signaling pathways under consideration are relevant for migraine, potentially serving as the
foundation for future investigations.

## Key facts

- **NIH application ID:** 10072464
- **Project number:** 1R21NS118852-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** David D McKemy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,500
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072464

## Citation

> US National Institutes of Health, RePORTER application 10072464, The role of TRPM8 and artemin in migraine (1R21NS118852-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072464. Licensed CC0.

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