Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis

Vol. 210, No. 2, 2005

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Selected Topics on Clinical Dermatology in Switzerland - Past and Present
Dedicated to Theo Rufli
Editors: A.J. Bircher, Basel; S.A. Buechner, Basel; P.H. Itin, Aarau/Base

Paper

Changes of Epidermal Mu-Opiate Receptor Expression and Nerve Endings in Chronic Atopic Dermatitis
M. Bigliardi-Qi^a,b, B. Lipp^a, L.T. Sumanovski^a,b, S.A. Buechner^a, P.L. Bigliardi^a,c

Departments of
^aDermatology and
^bResearch, University of Basel, Basel, and
^cDepartment of Dermatology, Kantonsspital Schaffhausen, Schaffhausen, Switzerland

Address of Corresponding Author

Dermatology 2005;210:91-99 (DOI: 10.1159/000082563)

Key Words

µ-Opiate receptor internalization
Epidermis
Atopic dermatitis
Peripheral nerve endings
Pruritus
Itch

Abstract

There is increasing evidence that neuropeptides such as a substance P, neurotrophins or beta -endorphin, an endogenous agonist for µ-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. µ-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of µ-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of µ-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the µ-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the 'intensity' and 'pattern' hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that 'itch' is elicited in the epidermal unmyelinated nerve C-fibers and 'pain' in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the 'layer hypothesis'.

Author Contacts

Paul Bigliardi
Kantonsspital Schaffhausen, Verwaltungsgebäude
CH-8200 Schaffhausen (Switzerland)
Tel. +41 52 620 22 19, Fax +41 52 620 22 42
E-Mail paul.bigliardi@kssh.ch

Article Information

Number of Print Pages : 9
Number of Figures : 7, Number of Tables : 0, Number of References : 35

Medline Abstract (ID 15724090)

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