Nerve growth factor mediates the incision-induced upregulation of ASIC3 via phosphoinositide 3–kinase/protein kinase B. Western blot analysis indicated that increases in ASIC3 (A) and phosphorylated protein kinase B (B) expression occurred at 4 h after incision. The overexpression of ASIC3 and phosphorylated protein kinase B was blocked by intraplantar administration of a nerve growth factor antibody. The expression of total protein kinase B was not changed (B). n = 6 per group; *P < 0.05, **P < 0.01 versus sham, #P < 0.05 versus vehicle; as determined by one-way ANOVA followed by Dunnett’s test. The expression of ASIC3 and phosphorylated protein kinase B in the skin was increased at 4 h and 1 d after intraplantar administration of nerve growth factor (C). n = 5 per group; *P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle; as determined by one-way ANOVA followed by Dunnett’s test. Western blot analysis indicated that the increase in ASIC3 four hours after incision was inhibited by intraplantar administration of the phosphoinositide 3–kinase inhibitor LY294002 (D). The data are shown as the mean ± SD. n = 4 per group; *P < 0.05 versus sham; as determined by one-way ANOVA followed by Dunnett’s test. Pretreatment with LY294002 decreased the cumulative pain score (E) and increased the withdrawal threshold (F) to von Frey filaments at postoperative hour 4 and on postoperative day 1 after plantar incision. LY294002 increased the withdrawal latency to radiant heat at postoperative hour 4 only (G). n = 6 in the incision group, n = 9 in the incision + LY294002 group; *P < 0.05, **P < 0.01 versus incision, as determined by two-way repeated-measures ANOVA followed by Tukey’s post hoc test. Akt, protein kinase B; p-Akt, phosphorylated protein kinase B; ASIC3, acid-sensing ion channel 3.