Resiniferatoxin (RTX) attenuates postsurgical mechanical allodynia when given preemptively (red line) or after the establishment of hypersensitivity (orange line). Data are plotted as median with IQR. (A) A range of filaments were assessed including a 0.4-g filament, which did not induce a behavioral response. (B–E) Preemptive resiniferatoxin (n = 6, red line) attenuated behavioral responses to 1-g, 2-g, 4-g, and 6-g filaments, indicating a reduction in postincisional mechanical allodynia with resiniferatoxin treatment. (*P < 0.05, two-way repeated measures ANOVA with post hoc comparison to vehicle control with Holm-Sidak adjustment). Resiniferatoxin was given 1 day after surgical incision (n = 6, orange line) with testing at least 2 h after intraplantar resiniferatoxin injection. Animals demonstrated attenuation of mechanical allodynia compared to vehicle control (†P < 0.05, two-way repeated-measures ANOVA with post hoc comparison to vehicle control with Holm-Sidak adjustment). Vehicle-treated control n = 5. IQR = interquartile range; POD = postoperative day.