Role of kappa-opioid and mu-opioid receptors in pruritus: Peripheral and central itch circuits - PubMed (original) (raw)

. 2022 Dec;31(12):1900-1907.

doi: 10.1111/exd.14669. Epub 2022 Sep 23.

Affiliations

Role of kappa-opioid and mu-opioid receptors in pruritus: Peripheral and central itch circuits

Brian S Kim et al. Exp Dermatol. 2022 Dec.

Abstract

Modern genetic approaches in animal models have unveiled novel itch-specific neural pathways, emboldening a paradigm in which drugs can be developed to selectively and potently target itch in a variety of chronic pruritic conditions. In recent years, kappa-opioid receptors (KORs) and mu-opioid receptors (MORs) have been implicated in both the suppression and promotion of itch, respectively, by acting on both the peripheral and central nervous systems. The precise mechanisms by which agents that modulate these pathways alleviate itch remains an active area of investigation. Notwithstanding this, a number of agents have demonstrated efficacy in clinical trials that influence both KOR and MOR signalling. Herein, we summarize a number of opioid receptor modulators in development and their promising efficacy across a number of chronic pruritic conditions, such as atopic dermatitis, uremic pruritus and beyond.

Keywords: afferent; atopic; dermatitis; dynorphins; histamine; neurons; opioid; receptors; spinal cord.

© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.

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Conflict of interest statement

Brian Kim is a consultant for Outlook for iOS, AbbVie, ABRAX Japan, Almirall, Amagma, Arcutis, Arena, AstraZeneca, Bellus Health, Blurprint Medicines, Boehringer Ingelheim, Bristol Myers Squib, Cara Therapeutics, Clexio Biosciences, Cymabay, Daewoong Pharmaceuticals, Eli Lilly, Escienct, Evommune, Galderma, Genentech, GlaxoSmithKline, Granular Therapeutics, Janssen, Kiniksa, Incyte, LEO Pharma, Maruho, Pfizer, Novartis, OM Pharma, Recens Medical, Regeneron, Sanofi Genzyme, Septerna, Third Harmonic, Trevi Therapeutics, Veradermics, and has received research grants for Cara Therapeutics and LEO Pharma. Saadet Inan, Jacek C. Szepietowski have no conflicts of interest. Sonja Ständer is an investigator for Dermasence, Kiniksa, Galderma, GSK, Menlo Therapeutics, Novartis, Sanofi, Trevi Therapeutics and Vanda Pharmaceuticals, and is a consultant and/or member of the advisory board for Abbvie, Almirall, Beiersdorf, Bellus Health, Benevolent, Bionorica, Cara Therapeutics, Celgene, Clexio Biosciences, Escient, Galderma, Grünenthal, Kiniksa, Leo, Lilly, Menlo Therapeutics, Novartis, Pfizer, Sanofi, Trevi Therapeutics. P.G. Unna Academy, Vifor. Thomas Sciascia is an employee of Trevi Therapeutics and conducts pharmacological investigations with nalbuphine including clinical trials in pruritus subjects. He also has granted patents on the use of nalbuphine in the treatment of pruritus. has no conflicts of interest. Gil Yosipovitch is a Scientific Advisory Board member and consultant for Pfizer, Trevi Therapeutics, Kiniksa, Regeneron, Sanofi, Galderma, Novartis, Eli Lilly, LEO Pharma, Bellus and CeraVe and has received research funds from Pfizer, Kiniksa, LEO Pharma, Novartis, and Eli Lilly.

Figures

FIGURE 1

FIGURE 1

Central and peripheral mediators in chronic pruritus. KOR, kappa‐opioid receptor; MOR, mu‐opioid receptor

FIGURE 2

FIGURE 2

Imbalances of kappa‐ and mu‐opioid receptors in pruritic skin.

References

    1. Dhand A, Aminoff MJ. The neurology of itch. Brain. 2014;137(Pt 2):313‐322. -PubMed
    1. Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100(3):945‐982. -PMC -PubMed
    1. Ständer S, Steinhoff M, Schmelz M, Weisshaar E, Metze D, Luger T. Neurophysiology of pruritus: cutaneous elicitation of itch. Arch Dermatol. 2003;139(11):1463‐1470. -PubMed
    1. Ständer S, Schäfer I, Phan NQ, et al. Prevalence of chronic pruritus in Germany: results of a cross‐sectional study in a sample working population of 11,730. Dermatology. 2010;221(3):229‐235. -PubMed
    1. Yosipovitch G, Bernhard JD. Clinical practice. Chronic pruritus. N Engl J Med. 2013;368(17):1625‐1634. -PubMed

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