Fig. 3

Dural 2AT causes hyperalgesic priming to GTN. A Facial withdrawal thresholds in PAR2KO mice (n = 4) following treatment of 2AT, WT controls following treatment of 2AT (n = 4), and WT controls (n = 4) following administration of vehicle and subthreshold GTN. Note that there are 12 days between the last time point of 48 h on the left and the baseline for GTN administration, indicated by the broken x-axis (see Fig. 1C). Application of 2AT significantly decreased withdrawal thresholds in WT mice and enhanced hyperalgesic priming to GTN compared to WT mice treated with vehicle (†) and PAR2KO mice treated with 2AT (*). PAR2KO mice previously treated with 2AT were hypersensitive at 1 h following dural 2AT and GTN administration compared to vehicle treated mice (§). B Grimace scores of PAR2KO mice and their WT controls. 2AT significantly increased grimacing in the acute phase in WT mice. *,^†p < 0.05, **,^††p < 0.01, ***,^†††p < 0.001, ^††††p < 0.0001. Data are represented as mean ± SEM