Dermal mast cells play a central role in the incidence of scratching behavior in mice induced by multiple application of the hapten, 2,4,6-trinitrochlorobenzene.

Repeated application of 1% 2,4,6-trinitrochlorobenzene (TNCB) in acetone solution causes chronic skin inflammation in BALB/c mice. Associated scratching behavior gradually appeared, and chronic scratching behavior was established over 40 days after the initial application of TNCB. In order to explore the possible involvement of T cells and mast cells in the appearance of pruritus, we examined the response of athymic nude mice and genetically mast-cell-deficient mice. We could not detect either severe skin inflammation or immunoglobulin (Ig)E production in T-cell-deficient BALB/c nu/nu mice even after 80 days of TNCB treatment, whereas typical severe skin inflammation and IgE production were observed in mast-cell-deficient WBB6F1-W/Wv and WBB6F1-Sl/Sld mice. Furthermore, we observed persistent scratching behavior in WBB6F1-W/Wv mice, but not in BALB/c nu/nu and WBB6F1-Sl/Sld mice. Histological examination of TNCB-treated animals revealed the development of dermal mast cells in W/Wv mice but not in Sl/Sld mice. Degranulation of dermal mast cells was observed in the WBB6F1-W/Wv genotype, but most mast cells remained intact in TNCB-treated BALB/c nu/nu mice. These results suggest that mast cells play a pivotal role in the incidence of scratching behavior in this chronic pruritus model.