Figure 5.

GPR35 activation inhibits TRPA1-induced mechanical hypersensitivity. (A) (i) Example recording showing the sensitisation of the afferent response to ramp distension of the colon by ASP7663 in tissue from a wildtype mouse. (ii) Grouped data showing the change in afferent firing during ramp distension of the colon before and after ASP7663 application. Two-way repeated measures ANOVA. (iii) Grouped data showing the peak change in afferent firing during ramp distension of the colon before and after ASP7663 application. Two-tailed ratio-paired t test. (B) (i) Example recording showing the sensitisation of the afferent response to ramp distension of the colon by ASP7663 in tissue from a GPR35−/− mouse. (ii) Grouped data showing the change in afferent firing during ramp distension of the colon before and after ASP7663 application. Two-way repeated measures ANOVA. (iii) Grouped data showing the peak change in afferent firing during ramp distension of the colon before and after ASP7663 application. Two-tailed ratio-paired t test. (C) Example recording from tissue from a wildtype mouse showing the inhibition of ASP7663-induced afferent firing and sensitisation of the response to ramp distension by pretreatment with CS. (D) Example recording from tissue from a GPR35−/− mouse showing the loss of the inhibitory effect of CS on ASP7663-induced afferent firing and sensitisation of the response to ramp distension. (E) Grouped data showing the change in afferent firing during the third (post-ASP7663) ramp distension in tissue from wildtype mice treated with ASP7663 with or without CS. Two-way repeated measures ANOVA with Holm–Sidak post-hoc tests. (F) Grouped data showing the change in afferent firing during the third (post-ASP7663) ramp distension in tissue from GPR35−/− mice treated with ASP7663 with or without CS. Two-way repeated measures ANOVA with Holm–Sidak post-hoc tests. (G) Grouped data showing the change in afferent firing during the third (post-ASP7663) ramp distension in tissue from wildtype mice treated with ASP7663 with or without Zap. Two-way repeated measures ANOVA with Holm–Sidak post-hoc tests. (H) Grouped data showing the peak change in afferent firing during the third (postvehicle or -ASP7663) ramp distension. One-way ANOVA with Bonferroni post-hoc tests. CS, cromolyn; TRPA1, transient receptor potential ankyrin 1.