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Nalbuphine, a kappa opioid receptor agonist and mu opioid receptor antagonist attenuates pruritus, decreases IL-31, and increases IL-10 in mice with contact dermatitis.

Authors
  • Inan, Saadet1
  • Huerta, Alvaro T2
  • Jensen, Liselotte E2
  • Dun, Nae J3
  • Cowan, Alan4
  • 1 Center for Substance Abuse Research, Lewis Katz Medical School at Temple University, Philadelphia, PA, USA. Electronic address: [email protected]
  • 2 Department of Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  • 3 Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  • 4 Center for Substance Abuse Research, Lewis Katz Medical School at Temple University, Philadelphia, PA, USA; Department of Pharmacology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Dec 01, 2019
Volume
864
Pages
172702–172702
Identifiers
DOI: 10.1016/j.ejphar.2019.172702
PMID: 31568781
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Chronic itch is one of the disturbing symptoms of inflammatory skin diseases. Kappa opioid receptor agonists are effective in suppressing scratching in mice against different pruritogens. Nalbuphine, a nonscheduled kappa opioid receptor agonist and mu opioid receptor antagonist, has been in clinical use for post-operative pain management since the 1980s and recently has been in clinical trials for chronic itch of prurigo nodularis (https://www.trevitherapeutics.com/nalbuphine). We studied whether nalbuphine is effective against chronic scratching induced by rostral neck application of 1-fluoro-2,4-dinitrobenzene (DNFB), an accepted mouse model of contact dermatitis to study pruritoceptive itch. Mice were treated once a week with either saline or nalbuphine 20 min before the third, fifth, seventh, and ninth sensitizations with DNFB and the number of scratching bouts was counted for 30 min. Skin samples from the neck of mice at week 4 were used to measure protein levels and mRNA expressions of chemokines and cytokines. Different sets of mice were used to study sedation and anhedonic-like behavior of nalbuphine. We found that: nalbuphine (a) antagonized scratching in a dose- and time-dependent manner without affecting locomotion, b) decreased IL-31, and increased anti-inflammatory IL-10, and c) induced more elevations in the levels of CCL2, CCL3, CCL12, CXCL1, CXCL2, CXCL9, CXCL10, IL-1β, IL-16, TIMP-1, M-CSF, TREM-1 and M1-type macrophages compared to saline. Increases in chemokines and cytokines and M1 macrophages by nalbuphine suggest an inflammatory phase of healing in damaged skin due to scratching. Our data indicate that nalbuphine is an effective antipruritic in murine model of pruritoceptive itch. Copyright © 2019 Elsevier B.V. All rights reserved.

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