Migraine is a complex neurological disorder consisting of intense, unilateral throbbing head pain and often accompanied by nausea, vomiting, and photophobia/phonophobia. Migraine is the third most common disease in the world with an estimated prevalence of 14.7 percent. In the U.S., it has been estimated that over 36 million people suffer from either chronic or episodic migraine. Migraine pain likely results from disruption to the complex interactions between the meningeal tissues and trigeminal neural system. A key receptor found expressed in both meningeal and trigeminal tissues is the protease-activated receptor 2 (PAR2). We hypothesize that PAR2 is a critical receptor for the development of migraine pain. In our preliminary data we have shown that PAR2 activation results nociceptive behavior in our novel mouse migraine model.
In aim 1 we will test if serine protease or small molecule agonist mediated activation of PAR2 leads to migraine-like pain behavior in a novel mouse model.
In aim 2 we will determine if dural fibroblasts sensitize trigeminal afferents as a result of PAR2 activation in the trigeminal-meningeal system.
In aim 3 we will test if PAR2-induced migraine-like pain is dependent on signaling to translation machinery via eIF4E. This project will expand our understanding of the molecular events that cause migraine pain, identify a novel pathway for the treatment of migraine pain with clinical-translational potential, investigate PAR2 signaling changes in trigeminal sensory neurons that mediate the maintenance of migraine pain, and provide an excellent training opportunity for learning patch-clamp electrophysiology, calcium imaging, live cell imaging, and mouse grimace behavior.

Public Health Relevance

Migraine headache is a common disease affecting millions of people each year. This project investigates the contribution of protease activated receptor signaling in mediating the pain experienced during migraine using novel behavioral and pharmacological tools.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS096963-02
Application #
9259738
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Oshinsky, Michael L
Project Start
2016-09-01
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Texas-Dallas
Department
Type
Sch Allied Health Professions
DUNS #
800188161
City
Richardson
State
TX
Country
United States
Zip Code
75080
Hassler, Shayne N; Ahmad, Fatima B; Burgos-Vega, Carolina C et al. (2018) Protease activated receptor 2 (PAR2) activation causes migraine-like pain behaviors in mice. Cephalalgia :333102418779548