91AV

91AV Assistant Professor Colin Willis, Ph.D., was recently awarded a $50,000 Migraine Research Foundation grant to study the mechanisms of blood-brain barrier dysfunction in medication overuse headaches. 

Dr. Willis, of the 91AV Department of Biomedical Sciences, College of Osteopathic Medicine, is also on the faculty of 91AV Center for Excellence in the Neurosciences.

Migraine affects more than 36 million Americans - nearly 1 in 4 families - including 10 percent of school-age children. Fourteen million people experience attacks on a near daily basis. U.S. employers lose more than $13 million a year from lost work days.

The condition is characterized by a unilateral throbbing pain, often associated with aura, nausea, vomiting and photophobia.

Despite its position as one of the world's most disabling diseases and its serious social and economic consequences, migraine remains misunderstood. MRF is one of the only sources of seed money for research into its causes and treatments.

Research Background

Sumatriptan, and other triptan-based medications, are frequently prescribed to relieve migraine pain.

However, reports indicate that initially following sumatriptan administration, headache pain may transiently intensify and that frequent use of triptan-based medication over an extended period may increase the frequency of migraines in migraine sufferers.

This condition is termed medication overuse headache. The mechanisms responsible for migraine and medication overuse headache are poorly understood. Several studies suggest that changes in the integrity of the blood-brain barrier may play a key role.

The blood-brain barrier is essential for brain homeostasis and the correct functioning of the central nervous system. The blood-brain barrier is a highly regulated interface that separates the peripheral circulating blood supply from the central nervous system and allows controlled changes in vascular permeability.

In health, there may be a regulated temporary increase in permeability to allow increased access of nutrients and oxygen to the brain, but in diseases such as multiple sclerosis and stroke, there is disruption of blood-brain barrier integrity resulting in disturbance of central nervous system ion balance and vasogenic edema.

Migraine is a common symptom associated with multiple sclerosis, acute mountain sickness/oxygen deprivation and stress. In these conditions there is also a change in blood-brain barrier integrity. Therefore, Dr. Willis reasoned that transient blood-brain barrier dysfunction may increase the likelihood of headache attack. To test this hypothesis he will use a behavioral model of medication overuse headache to assess changes in blood-brain barrier marker protein expressions and vascular permeability in specific brain regions.

A better understanding of the role of the blood-brain barrier is fundamental to our understanding of how migraine pathophysiology develops and how chronic use of medications can impact these processes.

The research may also identify novel proteins and pathways that could lead to the development of more effective migraine medications.

The Migraine Research Foundation

The is a nonprofit organization dedicated to ending the debilitating pain of migraine by funding research into its causes and better treatment options and ultimately, to finding a cure. 

Dr. Willis' grant was one of seven grants that were selected for the year through a competitive process from an unprecedented 40 proposals received from 9 countries.

This year's grantees will explore innovative inquiries in the areas of pediatric migraine, chronic migraine, migraine in women, and basic science.  "We are thrilled with the caliber of the investigations in these proposals. They represent novel clinical and bench science approaches to unraveling the mysteries of migraine," said Cathy Glaser, co-founder and president of MRF.  "In just four years, we've awarded 23 grants to some of the most promising investigators - and we know they're going to make a difference."

"This year's recipients continue to demonstrate the highly innovative thinking which MRF encourages. The medical community is grateful to the foundation and the investigators it supports," said Dr. Joel Saper, founder of the Michigan Head Pain & Neurological Institute, Ann Arbor, MI, and chair of MRF's medical advisory board.

The MRF medical advisory board of distinguished scientists, chaired by Dr. Saper, also includes Dr. Rami Burstein (Harvard Medical School, Boston, Mass.), Dr. F. Michael Cutrer (Mayo Clinic, Rochester, Minn.), Dr. David W. Dodick (Mayo Clinic, Phoenix, Ariz.), Dr. Peter J. Goadsby (University of California at San Francisco, Calif.), Dr. Richard Lipton (Albert Einstein College of Medicine, Bronx, N.Y.), Dr. Fred Sheftell (New England Center for Headache, Stamford, Conn.), and Dr. Stephen D. Silberstein (Jefferson University Hospital, Philadelphia, Penn.).