Fig. 3. Repeated application of TTA-P2 alleviates thermal and mechanical hypersensitivity post-incision.

A. Time course showing pre-surgical baseline measurements to heat and mechanical stimuli determined two days before surgery, 2 h post-incision, and on two consecutive days, prior to intrathecal treatment (i.t.) injections. Heat and mechanical hypersensitivity was assessed 30, 60 and 120 min after TTA-P2 or vehicle was applied i.t. in a single group of animals. B. Lack of the antinociceptive effect of the first dose of TTA-P2 applied 2 h after plantar skin incision on heat nociception (n=6 animals in vehicle and n=10 animals in treatment group; two-way RM-ANOVA). C and D respectively, Significant antinocicpetive effects of consecutive doses applied at 24 and 48 h post-incision, on heat nociception; n=6 animals in vehicle groups and n=9 animals in treatment groups * P<0.05, ** P<0.01, Mann-Whitney test; repeated treatment 24 h post-incision: p=0.003 and p=0.026; two-way RM-ANOVA, repeated treatment 48 h post-incision: F(1,13)=9.75; p=0.008; interaction: p=0.8). E, F and G respectively, Significant antinociceptive effect of repeated i.t. application of TTA-P2 on mechanical hypersensitivity 2, 24 and 48 h post-(; n=6 animals in vehicle group and n-5-6 animals per post-incision group; * P<0.05, ** P<0.01, two-way RM-ANOVA; repeated treatment 2 h post-incision: F(1,10)=19.7; p=0.001; repeated treatment 24 h post-incision: F(1,10)=8.73; p=0.014; repeated treatment 48 h post-incision: F(1,9)=7.08; p=0.026). Each data point represents the mean ± SEM for incised paw. PWL = paw withdrawal latency; PWR = paw withdrawal response.