LC/E-BoNT/A showed a long-lasting prophylactic anti-nociceptive effect on acute nocifensive behavior induced by capsaicin, with the maximum amelioration observed on day 4 after neurotoxin injection into the right whisker pad. (A) Weight gained, (B) grooming, as the time each animal spent rubbing the injected facial area with its paws in a 20 min recorded period, (C) locomotor behavior assessed by the measurement of total distance walked, and (D) freezing time evoked by injection of capsaicin (2.5 µg in 20 µL) or vehicle 2 into rat right whisker pad, assessed at various days after administration of neurotoxin (75 units/kg). Data are expressed as mean + SEM (n = 10) and were analyzed by one-way ANOVA followed by Bonferroni’s post hoc test. ## p < 0.01, ### p < 0.001 vs. vehicle 1 → vehicle 2 group; * p < 0.05, ** p < 0.01, *** p < 0.001 vs. vehicle 1 → capsaicin group.