"Blood Brain Barrier Alterations Induced By Hypoxia, Pain or Stroke - Challenge to drug delivery". Pain or hypoxic stroke affects well over 200 million people a year in the U.S. alone and costs billions of dollars in medical treatment and lost productivity. To date many of the investigations concerning the blood brain barrier (BBB) and the delivery of therapeutics to the CNS to treat these pathologies have been performed in naive animals. It is increasingly clear that the BBB is not a static barrier, but can be modulated and challenged by a number of factors from the immune, neuronal , glial , endothelial and hormonal systems. During pain , hypoxia or stroke each of the neurovascular unit (NVU) cell types are activated. We are currently investigating specfic NVU cell types, BBB tight junction (TJ) proteins Claudin 5 and Occludin , P-gp and OATP transporter function and trafficking , and drug - drug interaction (DDI) challenges that are aleterd by pain, hypoxia or stroke (using preclinical models) to determine how these pathologies modify the delivery of therapeutic drugs to treat these pathologies.