Antinociceptive effect of (±)-CPP in monoarthritic rats. (A) Time-course of the antinociceptive effect of increasing doses of i.t. (±)-CPP (2.5, 5.0, 12.5, 25, 50, and 100 μg/rat). Vocalization thresholds were measured before (left arrow), and then 28 days after monoarthritis induction, and after a single injection of CPP. Open symbols, values from monoarthritic rats. Solid symbols, values from normal rats receiving saline under a similar protocol. The right arrow corresponds to CPP or saline injection. 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 (±)-CPP Treatment factor (F(6, 175) = 39.32; ANOVA P < 0.0001), as well as for the Time factor (F(5, 175) = 56.64; ANOVA P < 0.0001). Bonferroni multiple comparisons post hoc test showed that vocalization thresholds of all (±)-CPP treated rats (2.5, 5.0, 12.5, 25, 50, and 100 μg/rat) 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 four highest doses of (±)-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 < 0.05; **P < 0.01; ***P < 0.001; compared with monoarthritic rats receiving saline).