title: Targeting blood-brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery.
abstract: The blood-brain barrier (BBB) is the most significant obstacle to effective CNS drug delivery. It possesses structural and biochemical features (i.e., tight-junction protein complexes and, influx and efflux transporters) that restrict xenobiotic permeation. Pathophysiological stressors (i.e., peripheral inflammatory pain) can alter BBB tight junctions and transporters, which leads to drug-permeation changes. This is especially critical for opioids, which require precise CNS concentrations to be safe and effective analgesics. Recent studies have identified molecular targets (i.e., endogenous transporters and intracellular signaling systems) that can be exploited for optimization of CNS drug delivery. This article summarizes current knowledge in this area and emphasizes those targets that present the greatest opportunity for controlling drug permeation and/or drug transport across the BBB in an effort to achieve optimal CNS opioid delivery.
authors.affiliation: Department of Medical Pharmacology, College of Medicine, University of Arizona, 1501 N Campbell Avenue, PO Box 245050, Tucso, AZ, USA. pronald@email.arizona.edu
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ronaldson
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid