Vital role of the itch-scratch response in development of spontaneous dermatitis in NC/Nga mice

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Abstract
Background The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch–scratch response on the pathology of AD has not been precisely elucidated. Objectives To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv‐NC mice), which are known to be an animal model for human AD. Methods Capsaicin‐sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap‐NC mice), and the development of spontaneous dermatitis in the Cap‐NC mice was compared chronologically with that in Conv‐NC mice. Results Scratching behaviour was almost completely prevented in Cap‐NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap‐NC mice were lower than those in Conv‐NC mice. Immunological studies showed that the capability of spleen T cells to produce both T‐helper (Th) 1 (interferon‐γ) and Th2 [interleukin (IL)‐5 and IL‐13] cytokines was diminished in Cap‐NC mice. Furthermore, serum levels of IL‐18 were approximately twice higher in Conv‐NC mice than in Cap‐NC mice. Conclusions These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch‐associated scratching behaviour is an effective treatment for AD.