Stress reduces cutaneous inflammation in irritant and allergic contact dermatitis models. (a, b) To induce irritant contact dermatitis (ICD), both ears of one group of C57BL/J mice were treated topically with 20 μl of 0.03% phorbol 12-myristate 13-acetate (TPA). The ear thickness was measured with a digital caliper (Mitutoyo, Tokyo, Japan) 18 hours after oxazolone (Ox) or TPA application, and the results are presented in panel d. Frustration (action-restricted) stress was administered as described in Methods. (c, d) For acute allergic contact dermatitis (ACD), 5% Ox was applied topically once to the flank of C57BL/J mice. One week later, the ears of one group C57BL/J mice were topically treated with a single dose of 0.5% Ox. After TPA or Ox treatments, parallel groups of mice were kept individually in 5 × 11 × 4 cm box for 18 hours, to induce frustration (restraint model) (Youm et al., 2013). The two-tailed Student's t-test was used to determine significant differences.