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This article has been peer reviewed. It was published in: American Society of Regional Anesthesia & Pain Medicine.

Volume 45, Issue 9, 1 September 2020, Pages 688-695.

The published version is available at DOI: 10.1136/rapm-2020-101403

Copyright © American Society of Regional Anesthesia & Pain Medicine 2020.

Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See:


The blood-brain barrier (BBB) describes the unique properties of endothelial cells (ECs) that line the central nervous system (CNS) microvasculature. The BBB supports CNS homeostasis via EC-associated transport of ions, nutrients, proteins and waste products between the brain and blood. These transport mechanisms also serve as physiological barriers to pathogens, toxins and xenobiotics to prevent them from contacting neural tissue. The mechanisms that govern BBB permeability pose a challenge to drug design for CNS disorders, including pain, but can be exploited to limit the effects of a drug to the periphery, as in the design of the peripherally acting μ-opioid receptor antagonists (PAMORAs) used to treat opioid-induced constipation. Here, we describe BBB physiology, drug properties that affect BBB penetrance and how data from randomized clinical trials of PAMORAs improve our understanding of BBB permeability.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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