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. 2021 Feb 9;11:523769. doi: 10.3389/fphys.2020.523769

Figure 4.

Figure 4

Area Under Curve (AUC) normalized with control (vehicle animals) for the effects of single or combined therapies of SN, LGZ, and PCM at different dosages against mechanical and heat hypersensitivities in rats with incisional pain (A,B), or in mice with carrageenan induced inflammatory pain (C,D). N = 6–8 animals, data were presented as mean ± SEM. Blue, red, or green lines represent the average AUCs of mechanical/heat thresholds for SN 80 mg/kg, LGZ 80 mg/kg, or PCM 100 mg/kg treatment, respectively. Filled circles indicating AUCs of drug combinations were larger than the average AUCs of effective single drug treatments (SN 80 mg/kg and LGZ 80 mg/kg). AUCs of drug combinations were compared with SN (at 10 or 20 mg/kg, **P < 0.01, ***P < 0.001, significant differences with specific groups were illustrated by respective representing colors), LGZ (at 10 or 20 mg/kg, #P < 0.05, ##P < 0.01, ###P < 0.001, significant differences with specific groups were illustrated by respective representing colors); or PCM (at 10 or 30 mg/kg, ++P < 0.01, +++P < 0.001, illustrated by respective representing colors), using Bonferroni's multiple comparisons test following ANOVA. Gray shaded area marked the significant (and most effective) dosage combination for the combined drug therapies.