Spontaneous scratching behaviour in DS-Nh mice as a possible model for pruritus in atopic dermatitis.
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.
Yoshioka
T
T
Shionogi Discovery Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan. takeshi.yoshioka@shionogi.co.jp
Hikita
I
I
Asakawa
M
M
Hirasawa
T
T
Deguchi
M
M
Matsutani
T
T
Oku
H
H
Horikawa
T
T
Arimura
A
A
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
D000982:Antipruritics; D039563:Histamine H1 Antagonists, Non-Sedating; D007073:Immunoglobulin E; D017336:Loratadine; D006632:Histamine; D020932:Nerve Growth Factor