Capsaicin treatment causes acute algetic responses and a subsequent analgesic effect. (A) Time course of 90 min following intraplantar injection of 25 (n = 9 rats), 50 (n = 16) and 100 μg (n = 12) capsaicin or vehicle (n = 14) (p < 0.001 for 25 μg, p < 0.001 for 50 μg and p < 0.001 for 100 μg capsaicin versus vehicle control group, ANOVA). The quantitative analysis showed that the number of flinches was increased at capsaicin-injected hindpaw. (B) Intraplantar pre-injection of 100 μg capsaicin (n = 13) but not 50 μg capsaicin (n = 8) or vehicle (n = 12) induced an analgesic effect in the pain model induced by 2% formalin (p < 0.001 for 100 μg capsaicin versus vehicle group, ANOVA). The time course showed that the inhibitory effect of capsaicin on the formalin-induced flinch in the phase II was lasted for 30 min. The number of flinches in the phase I and phase II was reduced in the rats with capsaicin pre-treatment. (C) Intraplantar pre-injection of 10 μg capsaicin (n = 15) reduced the licking time of mice induced by 2% formalin, compared to vehicle group (n = 15) (p < 0.001, ANOVA). The licking time in both phase I and phase II was decreased in mice. Data are shown as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, versus vehicle group.