Scratching behavior in NC/Nga mice with dermatitis: Involvement of histamine-induced itching

Background: Itching, a typical symptom in dermatitis, including atopic dermatitis (AD), leads to scratching. In the present study, we investigated whether histamine-induced itching is involved in scratching behavior seen in NC/Nga (NC) mice, in which AD-like dermatitis is induced spontaneously. Methods: The severity score of dermatitis, the number of scratches, histamine content, activity of the histamine-forming enzyme histidine decarboxylase (HDC), the number of mast cells and the effect of histamine receptor antagonists were examined. Results: We found two types of scratching behavior in NC mice, one of a short duration (0.3-1.0 s) and the other of a longer duration (over 1.0 s). The number of short scratchings and HDC activity increased with age (4-13 weeks) in parallel with the severity of dermatitis in NC mice raised in conventional surroundings. The number of longer-duration scratchings had increased before any apparent development of dermatitis and this type of scratching behavior increased at 13 weeks, as did histamine content and mast cell number in the skin. There were no changes in these parameters in NC mice raised in specific pathogen-free surroundings during the experimental period. Chlorpheniramine (a histamine H₁ receptor antagonist), but not histamine H₂ and H_3/4 receptor antagonists, decreased the number of short scratchings. None of the histamine receptor antagonists decreased the number of long scratchings, whereas tacrolimus reduced both short and long scratching behavior. Conclusions: The findings of the present suggest that histamine produced by enhanced HDC activity is involved in the induction of short scratchings in NC mice.