title: Spontaneous scratching behaviour in DS-Nh mice as a possible model for pruritus in atopic dermatitis.
abstract: Itching is one of the major clinical symptoms in atopic dermatitis (AD) and complicates the management of this pathological condition. An animal model of AD-like pruritus would contribute to a better understanding of AD and could lead to the development of safe and effective antipruritic agents. DS non-hair (DS-Nh) mice raised under conventional conditions spontaneously develop pruritus, which is associated with a dermatitis similar to human AD. There is a significant positive correlation between disease severity and the period of scratching behaviour in DS-Nh mice. In the present study, we found that levels of histamine and nerve growth factor (NGF) in serum and/or skin tissue were higher in DS-Nh mice with AD-like dermatitis than in age-matched mice without dermatitis. The histopathological data indicated that nerve fibres extend into and mast cells infiltrate the surrounding area of the skin lesion. NGF production by XB-2 cells, which was derived from mouse keratinocytes, was enhanced by histamine via the H1 receptor. We also found that prolonged treatment with an H1-antagonist was effective against pruritus through depression of the production of NGF, which is thought to be generated by keratinocytes. We conclude that DS-Nh mice can serve as a suitable model for gaining a better understanding of pruritus in AD, and that prolonged treatment with an H1-antagonist may be beneficial in patients with AD-associated pruritus.
authors.affiliation: Shionogi Discovery Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan. takeshi.yoshioka@shionogi.co.jp
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: I
authors.initials: I
authors.lastname: Hikita
authors.forename: M
authors.initials: M
authors.lastname: Asakawa
authors.forename: T
authors.initials: T
authors.lastname: Hirasawa
authors.forename: M
authors.initials: M
authors.lastname: Deguchi
authors.forename: T
authors.initials: T
authors.lastname: Matsutani
authors.forename: H
authors.initials: H
authors.lastname: Oku
authors.forename: T
authors.initials: T
authors.lastname: Horikawa
authors.forename: A
authors.initials: A
authors.lastname: Arimura
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000627:therapeutic use; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000097:blood; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D017336:Loratadine / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
chemical_list: D000982:Antipruritics; D039563:Histamine H1 Antagonists, Non-Sedating; D007073:Immunoglobulin E; D017336:Loratadine; D006632:Histamine; D020932:Nerve Growth Factor