Fig. 1.
Mice without TIP39 signaling develop less thermal hypersensitivity and tactile allodynia following nerve injury than WT. Thermal and mechanical hindpaw withdrawal thresholds were measured over time following PNL of PTH2R-KO (A–F) and TIP39-KO (G–L) mice and WT littermates. WT developed thermal hypersensitivity that lasted for 20 (A; F7, 56 = 5.8; P < 0.001) to 30 d (G; F7, 49 = 5.4; P < 0.01). PTH2R-KO (B) and TIP39-KO (H) did not develop significant thermal hypersensitivity. Area under the curve measurements for the total experiment duration showed significant differences between thermal sensitivity of WT and both PTH2R-KO (C; P < 0.05, n = 7–9 per group) and TIP39-KO (I; P < 0.01, n = 7–8 per group). PNL caused mechanical hypersensitivity (allodynia) in WT that lasted from 60 (D; F7, 56 = 7.8; P < 0.001) to at least 80 (J; F7, 49 = 11.5; P < 0.001) days, the experiment’s endpoint. Mechanical withdrawal thresholds of PTH2R-KO mice did not significantly differ from baseline at any time (E). TIP39-KO mice developed allodynia lasting 30 d (K; F7, 49 = 3.1; P < 0.001). Area under the curve measurements showed that PTH2R-KO (F; P < 0.001, n = 7–9 per group) and TIP39-KO (L; P < 0.001, n = 7–8 per group) developed significantly less mechanical sensitivity than WT. Dotted lines indicate time over which withdrawal thresholds differed significantly from the presurgical value. P values in the legend correspond to the effect of time in the ANOVA. Symbols above the columns are from the post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001.