Antinociceptive effect of PPF in monoarthritic rats. (A) Time course of the antinociceptive effect of daily repeated injections of PPF in monoarthritic rats. Vocalization thresholds were measured before (left arrow), and then 28 days after monoarthritis induction, and 10 days after repeated injection of PPF (right arrows) (Time 0). Empty symbols represent values from monoarthritic rats. Solid symbols represent values from normal rats receiving saline under a similar protocol. Values are expressed as mean ± standard error of the mean (SEM); n = 6 rats per group. Two-way ANOVA indicates a significant effect for the PPF treatment factor (F(4, 125) = 132.20; ANOVA P < 0.0001) as well as for the time factor (F(4, 125) = 7.55; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of rats receiving the three highest doses of PPF (10, 30, and 100 μg/rat) were significantly higher (P < 0.05) than the corresponding thresholds of saline-treated animals (symbols omitted). In addition, Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of rats after receiving the highest doses of PPF were significantly higher (*P < 0.05) than the threshold measured before monoarthritis induction. (B) Ordinate indicates percentage antinociception obtained from the area under the time-course curves from (A) (see Materials and methods). Data are expressed as mean ± standard error of the mean (SEM), and were analyzed by using one-way ANOVA followed by Tukey-Kramer multiple comparisons test (***P < 0.001, compared with monoarthritic rats receiving saline).