Atopic dermatitis model of itching behavior in hairless mice

Abstract

In atopic dermatitis (AD), severe itching and scratching not only impacts the patient's quality of life, but also exacerbates the disease; however, the precise underlying mechanisms of itching in AD remain elusive. We have previously reported a special diet-induced, mouse model of AD. This article reviews the characteristics of the model, and the chronological and pharmacological analyses of the pathology. HR-1 hairless mice fed a commercial special diet, HR-AD, but not a normal diet, showed scaly dry red skin resembling AD. To evaluate the degree of itching, spontaneous scratching was analyzed. As a result, scratching with long duration was observed in HR-AD-fed mice, as confirmed by prolongation of duration of one scratching bout. Chronological analysis of the pathologies in HR-AD-fed mice revealed that the prolonged scratching was coincident with the development of skin barrier dysfunction, while skin inflammation with recruitment of inflammatory cells, such as CD4+ T cells, eosinophils, and mast cells, and serum IgE elevations apparently followed the prolonged scratching. Epidermal nerve sprouting was detected almost coincidently with the prolonged scratching. Pharmacological analysis of the scratching behavior indicated that the prolonged scratching was suppressed by a μ-opioid receptor antagonist, but not by antihistamine, similar to AD patients. Although treatment with corticosteroid suppressed the skin inflammation, it was not effective against the prolonged scratching, the dry skin symptoms, and the epidermal nerve sprouting. Petrolatum ointment inhibited the prolonged scratching during the amelioration of skin barrier dysfunction. Furthermore, the barrier disrupted-dry skin was alleviated by oral administration of essential fatty acid, linoleic acid (LA), suggesting that LA deficiency appears to be responsible for the symptoms. Taken together, these findings suggest that skin barrier dysfunction is closely associated with the development of AD-like pruritus in this model.