FIGURE 4.
Intraperitoneal injection of Z944 reverses CFA‐mediated tactile allodynia in both sexes, in a dose‐dependent manner. (a) Paw withdrawal threshold, in grams, of adult male SD rats before (Day 0) and 1, 2, and 3 days following a hindpaw injection of either saline or CFA. Timepoints 20–140 min are following an i.p. injection of either 10 mg·kg−1 Z944 or vehicle 3 days post‐CFA injection (n = 9 animals for saline/vehicle and CFA/vehicle; n = 10 for saline/ mg·kg−1 Z944 and CFA/10 mg·kg−1 Z944). The effect of Z944 on CFA‐induced tactile allodynia (dark blue) was determined with a one‐way repeated measures ANOVA (P<.05), with Bonferroni post hoc comparisons to the Day 3 post‐CFA injection baseline paw withdrawal threshold. (b) Percent anti‐allodynia resulting from injection of either vehicle or 10 mg·kg−1 Z944 in CFA injected male SD rats (p = 4.9 × 10−6, Mann–Whitney unpaired t‐test, n = 9 animals for vehicle and 10 animals for Z944). Measures taken 80 min post‐i.p. injection. (c) Paw withdrawal threshold, in grams, of adult female SD rats before (Day 0) and 1, 2, and 3 days following hindpaw injection of either saline or CFA. Timepoints 20–140 min are following i.p. injection of either 10 mg·kg−1 Z944 or vehicle 3 days post‐CFA injection (n = 10 animals for all groups). The effect of Z944 on CFA‐induced tactile allodynia (dark pink) was determined with a one‐way repeated measures ANOVA (P< .05), with Bonferroni post hoc comparisons to the Day 3 post‐CFA injection paw withdrawal threshold. (d) Percent anti‐allodynia resulting from injection of either vehicle or 10 mg·kg−1 Z944 in CFA injected female SD rats (p = 3.6 × 10−6, Mann–Whitney unpaired t‐test, n = 10 animals for vehicle, 10 animals for Z944). Measures taken 80 min post‐i.p. injection. (e) Paw withdrawal threshold, in grams, of adult male SD rats before (Day 0) and 1, 2, and 3 days following a hindpaw injection of either saline or CFA. Timepoints 20–140 min are following i.p. injection of either 1, 3, or 10 mg·kg−1 Z944 or vehicle 3 days post‐CFA injection (n = 10 animals for all groups). (f) Percent anti‐allodynia resulting from injection of either vehicle (0 mg·kg−1 Z944) or 1, 3 or 10 mg·kg−1 Z944 in CFA injected male SD rats. Measures taken 80 min post‐i.p. injection. All error bars represent mean ± SEM. *P < .05 for all post hoc comparisons