Figure 4.

C781 blocks and also reverses the effects of neutrophil elastase, an endogenous PAR2-cleaving enzyme, up to 60 minutes poststimulus. Baseline (BL) paw withdrawal thresholds and grimace scores for male and female ICR mice were obtained before hind paw injection with neutrophil elastase (NE) and C781 intraperitoneal injection. C781 (10 and 30 mg/kg i.p.) was injected (A and B) 30 minutes before, (C and D) 30 minutes after, (E and F) 60 minutes after, and (G and H) 90 minutes after NE (10 units) paw injection, and (A, C, E, G) von Frey withdrawal thresholds and (B, D, F, H) grimace scores were each assessed after the NE injection. For the experiment injecting C781 60 minutes after NE, the 1 hour time point was skipped since it coincided with C781 injection time. In the “C781 30 minutes before NE” experiment, the C781 10 mg/kg group had n = 4 females and n = 3 males, the C781 30 mg/kg group had n = 3 females and n = 4 males, and the Vehicle group had n = 3 females and n = 4 males. In the “C781 30 minutes after NE” experiment, the C781 10 mg/kg group had n = 4 females and n = 3 males, the C781 30 mg/kg group had n = 3 females and n = 4 males, and the Vehicle group had n = 2 females and n = 5 males. In the “C781 60 minutes after NE” experiment, the C781 10 mg/kg group had n = 2 females and n = 3 males, the C781 30 mg/kg group had n = 2 females and n = 3 males, and the Vehicle group had n = 3 females and n = 2 males. In the “C781 90 minutes after NE” experiment, the C781 10 mg/kg group had n = 3 females and n = 3 males, the C781 30 mg/kg group had n = 3 females and n = 3 males, and the Vehicle group had n = 4 females and n = 4 males. *P < .05, **P < .01, ***P < .001, ****P < .0001. For paw withdrawal threshold and grimace scores, repeated measures 2-way ANOVA with Dunnett post-test was used. All group mean comparisons were made to the mean of the Vehicle group.