Morphine acts on spinal dynorphin neurons to cause itch through disinhibition

Nguyen, E., Lim, G., Ding, H., Hachisuka, J. , Ko, M.-C. and Ross, S. E. (2021) Morphine acts on spinal dynorphin neurons to cause itch through disinhibition. Science Translational Medicine, 13(579), eabc3774. (doi: 10.1126/scitranslmed.abc3774) (PMID:33536279)

Abstract

Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. Here, we used animal models and show that neuraxial morphine causes itch through neurons and not mast cells. In particular, we found that spinal dynorphin (Pdyn) neurons are both necessary and sufficient for morphine-induced itch in mice. Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hachisuka, Dr Junichi
• Authors: Nguyen, E., Lim, G., Ding, H., Hachisuka, J., Ko, M.-C., and Ross, S. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Science Translational Medicine
• Publisher: American Association for the Advancement of Science
• ISSN: 1946-6234
• ISSN (Online): 1946-6242
• Published Online: 03 February 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Science Translational Medicine 13(579): eabc3774
• Publisher Policy: Reproduced in accordance with the publisher copyright policy