The broad objective of this application is to identify neural mechanisms that cause migraineurs to seek sanctuary in the dark during attacks in effort to escape what they describe as "my head hurts more and I feel worse when I am exposed to light". The long-term objectives are to identify the impact of light on sensory, affective and autonomic neurological functions during migraine (human study), and discover the neural pathways through which lights alter these functions (animal study). Leading up to this grant proposal are years of listening to patients'testimonies which taught us that exposure to different kind of lights can trigger different symptoms in migraineurs with normal eyesight as compared to blind and color-blind migraineurs. Based on what we heard, we postulated that exacerbation of headache by light is one of many reasons why migraineus seek the dark during migraine and that different colors of lights have the capacity to trigger different neurological symptoms. Mechanistically, we hypothesized that during migraine, activity of neurons in brain regions that mediate different aspects of sensory, emotional, and autonomic responses to pain is modulated by both headache and light through signals transmitted to them from the spinal trigeminal nucleus and the optic nerve. In the clinical study, we will determine the effects of different colos of light on the intensity of migraine headache and its many associated symptoms. Two groups of migraineurs (normal eyesight and visually-impaired) and a control group will be expose to different intensities of white, blue, green, yellow and red lights (delivered through an FDA-approved photic stimulator) when they are pain-free and during an attack. Data analysis and interpretation will include strength of electroretinography and visual evoked potential signals (waveforms) as well as documentation of sensory, affective and physiological changes. In the animal study, we will determine whether neurons that play a role in the neurological symptoms that are altered by light in patients receive direct input from the retina and brain areas involved in the transmission of migraine headache. These studies will combine psychophysical observations in human subjects with tract-tracing, immunohistochemical, molecular and physiological techniques in animals.

Public Health Relevance

Photophobia often renders migraineurs dysfunctional as they are force to seek dark environment. The proposed research holds the key to the development of novel therapeutic strategies for preventing photophobia during migraine. The findings are also likely to advance our understanding of photophobia in individuals diagnosed with different types of retinal degenerative diseases, thus leading us a step closer to alleviating it.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS079678-03
Application #
8694112
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (02))
Program Officer
Porter, Linda L
Project Start
2012-07-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
$430,650
Indirect Cost
$183,150
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Moulton, Eric A; Becerra, Lino; Johnson, Adriana et al. (2014) Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. PLoS One 9:e95508
Files, Julia A; Schwedt, Todd J; Mayer, Anita P et al. (2014) Imploding and exploding migraine headaches: comparison of methods to diagnose pain directionality. Headache 54:1010-8
Kam-Hansen, Slavenka; Jakubowski, Moshe; Kelley, John M et al. (2014) Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 6:218ra5
Borsook, D; Erpelding, N; Lebel, A et al. (2014) Sex and the migraine brain. Neurobiol Dis 68:200-14
Burstein, Rami; Zhang, XiChun; Levy, Dan et al. (2014) Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains. Cephalalgia 34:853-69
Zhang, XiChun; Jakubowski, Moshe; Buettner, Catherine et al. (2013) Ezogabine (KCNQ2/3 channel opener) prevents delayed activation of meningeal nociceptors if given before but not after the occurrence of cortical spreading depression. Epilepsy Behav 28:243-8
Kagan, R; Kainz, V; Burstein, R et al. (2013) Hypothalamic and basal ganglia projections to the posterior thalamus: Possible role in modulation of migraine headache and photophobia. Neuroscience 248C:359-368
Noseda, Rodrigo; Burstein, Rami (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain 154 Suppl 1:S44-53