Pain and the blood-brain barrier: Obstacles to drug delivery

Delivery of drugs across the blood-brain barrier has been shown to be altered during pathological states involving pain. Pain is a complex phenomenon involving immune and centrally mediated responses, as well as activation of the hypothalamic-pituitary-adrenal axis. Mediators released in response to pain have been shown to affect the structure and function of the blood-brain barrier in vitro and in vivo. These alterations in blood-brain barrier permeability and cytoarchitecture have implications in terms of drug delivery to the central nervous system, since pain and inflammation have the capacity to alter drug uptake and efflux across the blood-brain barrier. An understanding of how blood-brain barrier and central nervous system drug delivery mechanisms are altered during pathological conditions involving pain and/or inflammation is important in designing effective therapeutic regimens to treat disease.