Comparative Study on Different Skin Pruritus Mouse Models

Abstract

The animal model is an important tool to study the mechanism of disease formation. Different animal models of pruritus have been adopted based on the purpose of researchers in the study of the itching mechanism. Although the symptoms of various models are quite different, scratching behavior is a key indicator. Therefore, it is necessary to find an animal model that can quickly induce animal scratching and maintain the stability of scratching behavior. In this study, we compared animal models of pruritus induced by four substances and found that the scratching behavior of mice induced by urushiol not only reached the plateau stage quickly but also showed more stability in the plateau phase than that induced by 2,4-dinitrofluorobenzene, oxazolone, and imiquimod. Meanwhile, in the animal model induced by urushiol, the changes of epidermal thickening and inflammatory cell aggregation were also more obvious. In addition, pruritus induced by urushiol is prevalent all over the world, especially in the United States and Europe, involving outdoor groups such as firefighters, forest loggers, and farmers. Therefore, we believe that the urushiol-induced animal model is an ideal choice for the study of the itch formation mechanism and the development of antipruritic drugs.

Keywords: allergic contact dermatitis; animal model; atopic dermatitis; pruritus; psoriasis; urushiol.

Figure 1

Itchy animals induced by pruritic irritant showed severe skin lesions. (A) The itch model was induced by different irritants [urushiol, 2,4-dinitrofluorobenzene (DNFB), and oxazolone]. The red arrow shows the treatment day with the pruritic irritant. (B) The psoriasis model was induced by imiquimod. (C) Different itch model mice showed obvious skin lesions on the neck compared with control mice. (D) Hematoxylin and eosin (H&E) painting of the skin slice on the 10th day. Model mice showed thickening to different degrees. Scale bar 20 μm. (E) Statistics of the epidermis thickness of the model mice and control mice. Significant difference is indicated by p-value (*compared with control mice; ^#compared with urushiol-induced model mice). ***p < 0.001, **p < 0.01, *p < 0.05; ^###p < 0.01.

Figure 2

Comparison of scratching bouts between different itch models. (A) Scratching bouts of the urushiol-induced mice were higher than those of oxazolone-induced mice and control mice. Significant difference is indicated by p-value (*shows urushiol-induced model mice compared with control mice; ^#shows urushiol-induced model mice compared with oxazolone group; ^$shows oxazolone group compared with control mice). (B) Pruritic behavior of the urushiol-induced mice was more obvious than that of DNFB-induced mice (^#shows urushiol-induced model mice compared with DNFB group; ^$shows DNFB group compared with control mice). (C) Compared with oxazolone, urushiol induced more obvious pruritus in 1 h (evoked scratching). (D) Compared with DNFB, there was no obvious difference in scratching bouts induced by urushiol in 1 h (evoked scratching). (E) Compared with oxazolone, urushiol induced more obvious pruritus in 24 h (spontaneous scratching). (F) There was an obvious difference in pruritus between DNFB and urushiol model mice. (G) Scratching bouts of the urushiol-induced mice were higher than those of IMQ-induced mice (^#shows urushiol-induced model mice compared with IMQ group; ^$shows IMQ group compared with control mice). (H) Scratching behavior of the different mice shown in 1 and 24 h on the first day. ***p < 0.001, **p <0.01, *p < 0.05; ^##p < 0.01, ^###p < 0.001; ^$p < 0.05.

Figure 3

Inflammatory cells mediated itch of the model mice. (A) Immunohistochemistry staining of the skin tissue. Toluidine blue staining of the model mice and control mice (upper figure), scale bar, 50 μm. Giemsa staining of the basophils and eosinophils, scale bar 25 μm (bottom of A). (B) Degranulation ratio of the model mice increased compared to control mice. (C) Inflammatory cells in skin tissue of the mice. ***p < 0.001, **p < 0.01, *p < 0.05.