Migraine is the most common neurological disorder, and affects over 10% of the population in any given year, with over half of these individuals reporting severe impairment. For many patients, a severe, even disabling, component of the migraine attack is photophobia, yet neuroscientists are just starting to investigate the underlying neurobiological mechanisms. The present application tests the overarching hypothesis that brainstem pain-modulating circuits, already implicated in migraine-related pain, also contribute to migraine-related photophobia. This hypothesis is based on the entirely unexpected observation that pain-modulating neurons in the rostral ventromedial medulla, the final output of an important brainstem pain-modulating system, develop photoresponsiveness in animal models of migraine headache, although they do not respond to light under normal conditions. In three Specific Aims using the nitroglycerin migraine model in the rat, we will document light-evoked activity in identified pain-modulating neurons and determine whether this is specific to migraine. We will also determine whether pain- modulating systems contribute to light aversion and light-induced pain enhancement. Finally, we will identify possible pathways through which light gains access to pain- modulating systems. The present proposal brings together electrophysiological and behavioral approaches to show how light engages pain-modulating systems to produce photophobia. These studies will provide insights into the neurobiological mechanisms of migraine-related photophobia, fundamental information critical for developing new migraine treatments.

Public Health Relevance

Migraine remains the most common neurological cause of disability, and current treatment options are ineffective for many patients. Migraine patients often avoid light, because light increases their headache pain. The work proposed in this application seeks to understand the role of the brain's own pain-modulating systems in photosensitivity during migraine, which should ultimately help us develop better treatments for migraine pain.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS082020-03
Application #
8694118
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Porter, Linda L
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97239