# Protease Activated Receptor Type 2 Targeting for Migraine Pain

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2021 · $481,084

## Abstract

Protease Activated Receptor Type 2 Targeting for Migraine Pain
PIs: Theodore Price, Gregory Dussor, Josef Vagner and Scott Boitano
ABSTRACT
 Migraine is the most common neurological disorder, the 3rd most common disease on earth, and the 8th most
disabling. Currently available treatments fail to effectively manage migraine in most patients. Development of
new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of
migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a
potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). Unfortunately the
evidence for this mechanism relies on imprecise pharmacological tools and lacks genetic validation. The central
hypothesis of this multi-PI research program is that PAR2 expression in nociceptors that project to the meninges
plays a key role in the pathogenesis of migraine pain by linking meningeal protease release to sensitization of
the trigeminal nociceptive system. The primary objectives of this proposal are to develop next generation PAR2
antagonists, to use these tools to validate PAR2 as a migraine pain target and to use mouse genetics to identify
the specific role of PAR2 expression in meningeal projecting nociceptors to migraine pain. Our first aim will be
to use our established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like
properties to probe PAR2 function in the context of a mouse model of migraine pain. Our second aim will use
pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in
migraine and signaling pathways engaged by PAR2 to evoke pain from the dura. Our final aim will use mouse
genetics to study the cell type-specific role of PAR2 in migraine pain. Our work will result in: 1) the discovery and
development of novel high potency antagonists for PAR2; 2) the development of an innovative new target for
migraine pain; and 3) provide the first genetic verification of the cell type-specific action of PAR2 in the pain
pathway. Taken together, successful studies will provide a preclinical rationale for the further development and
testing of PAR2 ligands for the treatment of migraine and other forms of pain.

## Key facts

- **NIH application ID:** 10161867
- **Project number:** 5R01NS098826-05
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Scott Boitano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,084
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161867

## Citation

> US National Institutes of Health, RePORTER application 10161867, Protease Activated Receptor Type 2 Targeting for Migraine Pain (5R01NS098826-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10161867. Licensed CC0.

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