Fig. 5: OAT1 is a functional mediator of inflammatory hypersensitivity.

a Timeframe of the experiment. b Sum of the stimulus-evoked responses to von Frey filaments. c 40% response threshold to mechanical force via von Frey filaments. d Stimulus intensity-response frequency curve for plantar von Frey mechanical stimulation 24 h after intraplantar CFA and final intrathecal siRNA injection (b–d, vehicle, siControl n = 8; siOat1 n = 7). e Timeframe of the experiment and f mechanical sensitivity following intraplantar CFA injection, represented as the average sum of the von Frey stimulus responses. g 40% response threshold to mechanical force via von Frey filaments. h Stimulus intensity-response frequency curve for plantar von Frey mechanical stimulation 24 h post intraplantar CFA (f–h, n = 8). i Cumulative durations of acute nocifensive behaviors evoked by intraplantar injection of capsaicin for mice intra-spinally injected as indicated (n = 8). j Mechanical hypersensitivity represented as the average sum of the von Frey stimulus responses. k 40% response threshold to mechanical force via von Frey filaments. l Stimulus intensity-response frequency curve for plantar von Frey mechanical stimulation 24 h after intraplantar CFA injection (j–l, n = 6). m Cumulative durations of acute nocifensive behaviors evoked by intraplantar injection of capsaicin for mice intra-spinally injected as indicated (n = 6). Statistically significant differences were determined by two-way ANOVA with repeated measures followed by Dunnett’s post hoc test (b, F_(3,60) = 461.2 F_(2,20) = 8.555; c, F_(3,60) = 177.7 F_(2,20) = 1.372; d, F_(5,100) = 98.07 F_(2,20) = 16.98; f, F_(8,168) = 429.9 F _(2,21) = 33.16; g, F_(8,168) = 152.3 F_(2,21) = 9.775; h, F_(5,105) = 103.7 F_(2,21) = 24.95); one-way ANOVA followed by Tukey’s post hoc test (i, F_(2,21) = 0.5614); two-way ANOVA with repeated measures followed by Dunnett’s post hoc test and multiple t-test with Holm-Sidak correction (j, F_(6,60) = 241.1 F_(1,10) = 34.17; k, F_(6,60) = 88.36 F_(1,10) = 6.260; l, F_{(7, 140)} = 168.6 F_{(3, 20)} = 92.58); or m, two-tailed Student’s t-test. ****p < 0.0001; ***p < 0.001; **p < 0.01; *p < 0.05; ^#p < 0.0001. Asterisks (*) refer to statistical comparisons between conditions and hashtags (^#) to comparisons relative to basal values in each condition. In bar graphs, each point represents the mean value derived from one independent mouse. Graphs represent mean ± SEM. See also Supplementary Figs. 5 and 6.