Fig. 8

Antipruritic actions of TPA023B in chronic itch models. a Oxazolone model of chronic atopic-like dermatitis. Scratching bouts after injection of TPA023B (1 mg kg⁻¹, i.p.) over time (left). Total numbers of scratching bouts between 15 and 210 min after TPA023B/vehicle administration (right). Unpaired two-sided t-test, n = 10 mice per group. b Same as a but dry skin model of dermatitis, n = 6 mice per group. c Lack of tolerance development after 10 day treatment with TPA023B (TPA, 1 mg kg⁻¹, i.p. once daily). Two-way ANOVA (pretreatment x treatment), F(1,1) = 0.96, P = 0.34. Two-sided t-test indicates similar antipruritic effects in vehicle and TPA023B pretreated mice, n = 6 (TPA/TPA), n = 5 for all other groups. d Dermatitis score. Chronic systemic treatment with TPA023B (1 mg kg⁻¹ i.p., once per day) starting on day 11 of oxazolone exposure. Oxazolone challenges were continued during TPA023B treatment every other day. Only mice with a dermatitis score of 5 or higher on day 11 were included. In TPA023B-treated mice the dermatitis score decreased from day 6 of treatment onwards (F(9,54) > 38.7; P < 0.026 to P < 0.001) (left), but remained almost constant in vehicle-treated mice (right). Mixed repeated measures ANOVA revealed a significant treatment x time interaction F(9,117) = 22.6; P < 0.001 for day 8 and 9 (⁺⁺⁺). Differences between both treatment groups were significant at day 8 and 9. ***P = 0.0009 and ****P < 00001. Photographs show the same mice before treatment (left) and after 9 days of treatment (right). e Chronic topical treatment (0.3 µM TPA023B in 100 µl, once per day). Left: total number of scratching bouts between 15 and 210 min after TPA023B on day 9 after treatment begin. Unpaired two-sided t-test, P = 0.97, n = 6 mice per group. Right: same as left but dermatitis score (mixed repeated measures ANOVA treatment × time interaction F(9,99) = 0.61; P = 0.78; n = 6 and 7, for vehicle and TPA023B, respectively). Error bars indicate s.e.m.