Antinociceptive effect of PPF/(±)-CPP combination in monoarthritic rats. (A) Time course of the antinociceptive effect of daily repeated injections of PFF followed by a single injection of (±)-CPP in monoarthritic rats. Vocalization thresholds were measured before (left arrow) and then 28 days after monoarthritis induction, and after 10 repeated and a single injection of PPF and (±)-CPP, respectively (right arrows) (Time 0). Open 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/(±)-CPP treatment factor (F(5, 180) = 51,78; ANOVA P < 0.0001) as well as for the time factor (F(5, 180) = 44.37; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of all PPF/(±)-CPP treated rats were significantly higher (P < 0.05) than the corresponding threshold 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/(±)-CPP 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 < 0.01; ***P < 0.001; compared with monoarthritic rats receiving saline).