TRESK KO mice are hyper-responsive to dural application of IScap. A, The number of V1-directed forepaw wiping and hindpaw scratching within the 2 h recording period in male mice. Baseline behaviors were recorded in all mice 7 d postsurgery. The next day, mice received dural application of vehicle (n = 5 WT and 4 KO mice) or IScap (n = 10 WT and 8 KO mice). The behaviors were recorded 0.5–2.5 h after the dural application. **p < 0.01, ***p < 0.001; two-way ANOVA with post hoc Bonferroni test. B, The number of V1-directed behaviors in female mice (n = 5 WT and 4 KO mice in the vehicle groups; n = 12 WT and 10 KO mice in the IScap groups). C, D, The duration of V1-directed forepaw wiping and hindpaw scratching within the 2 h recording period in male (C) and female (D) mice (same mice as in A and B). E, Scatter plots of the duration of V1-directed behavior (normalized to the baseline values in individual mice) in response to dural application of vehicle or IScap. Data from the male and female mice are combined. Data from vehicle-treated mice are pooled together (open black square and red circle indicate WT and KO mice, respectively). F, The Z score of individual IScap-treated mice, calculated as Z = (value – mean)/SD. Value is the normalized duration of individual IScap-treated mice in E. Mean and SD are calculated from the normalized duration of all vehicle-treated mice in E. G, The percentage of WT and KO mice that respond to dural application of IScap, using Z > 1 and Z > 2 (> mean duration + 1 × SD or + 2 × SD of vehicle-treated mice) as the threshold respectively. **p < 0.01, Fisher’s exact test between the corresponding WT and KO groups.