Blood Brain Barrier and Migraine: Effect on Therapy (Diversity Supplement)

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Project Summary Migraine is a primary headache disorder that affects women at a 3:1 ratio as compared to men which features a cyclical pattern of chronic pain attacks resulting from central sensitization of the trigeminal nervous system and various other neurovascular mechanisms to create a disease state wherein pain perception is intensely heightened. Migraine headaches are often triggered by environmental sensory stimuli, such as light and sound, wherein banal amounts of sensory input become noxious and induce headache suggesting that maladaptive association between the nociceptive and sensory processing networks could be the underlying cause. Neural damage leading to altered functional connectivity, increased production of inflammatory neuropeptides; and dysfunctional integration and processing of modality-specific sensory information are thought to be some mechanisms of migraine. Each of these is also implicated disruption of blood brain barrier homeostasis. Decreased integrity of the BBB can either increase or decrease the amount of xenobiotics entering the brain during disease providing a rational to study how therapeutic efficacy varies between the sexes during migraine. This proposal will determine if antimigraine blood to brain uptake differs between male and females because of physiological differences in the blood brain barrier by testing the hypothesis that sex hormone regulation of NHE1 through ERbeta in brain endothelial cells regulates sumatriptan blood-to-brain uptake in a sex dependent manner.