Fig. 2

Blocking S1PR1 signaling attenuated mechanical or thermal hyperalgesia caused by chronic NTG administration. A Timeline of drug administration and behavioral testing. B-C Repeated daily injection of W146 before NTG could prevented basal mechanical and thermal hyperalgesia of periorbital (B) and hindpaw (C, D). E–G post—treatment responses were assessed 2 h after NTG administration. W146 could attenuate NTG-triggered acute hyperalgesia. Two-way ANOVA and Bonferroni post hoc test analysis; *p < 0.05, **p < 0.01 and ***p < 0.001 compared with the Saline group; ^#p < 0.05, ^##p < 0.01 and ^###p < 0.001 compared with the NTG group. H-J Repeated daily injection of SEW2871 (a S1PR1 agonist) before NTG did not prevent basal hyperalgesia of periorbital (H) and hindpaw (I-J). Two-way ANOVA and Bonferroni post hoc test analysis; *p < 0.05, **p < 0.01 and ***p < 0.001 compared with the Saline group