Despite the high prevalence of migraine in the general population, understanding of the underlying mechanisms remains incomplete. A variety of theories focused on peripheral neural or neurovascular mechanisms have been put forward, but none of these has so far received conclusive experimental support. An alternative proposal is that migraine is triggered or at least maintained by a "central generator" in the brain itself.
Dr. Heinricher's laboratory recently showed that the rostral ventromedial medulla (RVM), a brainstem region with a well-characterized facilitating role in persistent pain states, contributes to hypersensitivity associated with migraine headache. The overarching hypothesis of the present proposal is that pain-facilitating neurons in the RVM contribute to hypersensitivity associated with migraine headache, and that the anti-migraine triptans exert their effects at least in part by an action in the RVM.
To test this, Dr. Heinricher's laboratory will record activity of identified RVM and trigeminal caudalis neurons in a model of migraine headache pain, dural inflammation. They will attempt to link activation of pain-facilitating "ON-cells" to sensitization of trigeminal neurons, and determine whether the anti-migraine action of triptans can at least in part by explained by direct or indirect effects on activation of RVM neurons.
Finally, although migraine is often described as a "vascular" headache, a simple relationship between headache pain and vascular changes has been elusive. The laboratory's new data point to the RVM as an important link between pain-modulation and cerebral blood flow. Dr. Heinricher's laboratory will determine the effects of manipulating specific RVM cell populations on cerebral blood flow, and test the role of those neurons in the vascular changes evoked by dural inflammation. The experiments described in this proposal will attempt to delineate a more complete theory of migraine headache pain by extending the idea of "central sensitization" in migraine headache to brainstem modulatory systems.
Dr. Heinricher's laboratory expects to find important support for the idea of a "central generator" in migraine headache pain, and to link brainstem pain-modulating systems to regulation of cerebral blood flow. Finally, these experiments should provide important insights into the mechanisms of action of anti-migraine triptans.
American Recovery and Reinvestment Act (ARRA)
The recently signed American Recovery and Reinvestment Act (ARRA) of 2009 provides $10.4 billion to the NIH to stimulate the U.S. economy by creating and retaining jobs and accelerating the pace of biomedical research.
National Institute of Neurological Disorders and Stroke (NINDS)
The mission of NINDS is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world.
Project Start: 20-JUL-2009
Project End: 30-JUN-2011
OHSU Neurosciences is one of the nation’s leading neurologic research and training programs and provides the most comprehensive care of neurologic illnesses in the Pacific Northwest. Our nationally recognized neurological programs and centers offer comprehensive clinical and surgical services that are available nowhere else in Oregon. Our leading-edge research and clinical trial opportunities ultimately provide new treatment options, earlier detection and improved quality of life for patients.