Figure 1.
Effects of intraperitoneal injections of different drugs on Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % maximal possible effect (MPE). One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 2.339; p = 0.0949), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 1.554; p = 0.2227), (C) Effects of intraperitoneal injections of morphine (0.32, 1 and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 11.75; p < 0.0001), (D) Effects of intraperitoneal injections of tramadol (1, 3.2 and 10 mg/kg) or vehicle (3% tween 80 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 9.916; p < 0.0001). Data are expressed as mean ± SEM of % MPE. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [CFA] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 1.
Effects of intraperitoneal injections of different drugs on Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % maximal possible effect (MPE). One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 2.339; p = 0.0949), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 1.554; p = 0.2227), (C) Effects of intraperitoneal injections of morphine (0.32, 1 and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 11.75; p < 0.0001), (D) Effects of intraperitoneal injections of tramadol (1, 3.2 and 10 mg/kg) or vehicle (3% tween 80 in saline) on CFA-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 9.916; p < 0.0001). Data are expressed as mean ± SEM of % MPE. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [CFA] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 2.
Effects of intraperitoneal injections of different drug combinations on CFA-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 9.492; p < 0.0001), main effect of combination (F(1,48) = 3.104; p = 0.0845), and main combination X drug dose interaction (F(3,48) = 1.186; p = 0.325), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 7.434; p = 0.0003), main effect of combination (F(1,48) = 1.105; p = 0.2984), and main combination X drug dose interaction (F(3,48) = 0.06326; p = 0.5775), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 6.288; p = 0.0011), main effect of combination (F(1,48) = 3.2; p = 0.9955), and main combination X drug dose interaction (F(3,48) = 0.06806; p = 0.5682), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 4.764; p = 0.0055), main effect of combination (F(1,48) = 0.006004; p = 0.9396), and main combination X drug dose interaction (F(3,48) = 0.1010; p = 0.9591). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [CFA] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 2.
Effects of intraperitoneal injections of different drug combinations on CFA-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 9.492; p < 0.0001), main effect of combination (F(1,48) = 3.104; p = 0.0845), and main combination X drug dose interaction (F(3,48) = 1.186; p = 0.325), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 7.434; p = 0.0003), main effect of combination (F(1,48) = 1.105; p = 0.2984), and main combination X drug dose interaction (F(3,48) = 0.06326; p = 0.5775), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 6.288; p = 0.0011), main effect of combination (F(1,48) = 3.2; p = 0.9955), and main combination X drug dose interaction (F(3,48) = 0.06806; p = 0.5682), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on CFA-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 4.764; p = 0.0055), main effect of combination (F(1,48) = 0.006004; p = 0.9396), and main combination X drug dose interaction (F(3,48) = 0.1010; p = 0.9591). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [CFA] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 3.
Effects of intraperitoneal injections of different drugs on STZ-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 5.474; p = 0.0043), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 2.102; p = 0.1225). (C) Effects of intraperitoneal injections of morphine (0.32, 1 and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 7.553; p = 0.0007), (D) Effects of intraperitoneal injections of tramadol (1, 3.2 and 10 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 18.59; p < 0.0001). Data are expressed as mean ± SEM of % MPE. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [STZ] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 3.
Effects of intraperitoneal injections of different drugs on STZ-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 5.474; p = 0.0043), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Main effect of treatment (F(3,28) = 2.102; p = 0.1225). (C) Effects of intraperitoneal injections of morphine (0.32, 1 and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 7.553; p = 0.0007), (D) Effects of intraperitoneal injections of tramadol (1, 3.2 and 10 mg/kg) or vehicle (3% tween 20 in saline) on STZ-induced changes in % MPE. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,28) = 18.59; p < 0.0001). Data are expressed as mean ± SEM of % MPE. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [STZ] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 4.
Effects of intraperitoneal injections of different drug combinations on STZ-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 7.855; p = 0.0002), Significant main effect of combination (F(1,48) = 8.748; p = 0.0048), and main combination X drug dose interaction (F(3,48) = 0.5447; p = 0.6541), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 13.61; p < 0.0001), main effect of combination (F(1,48) = 0.7796; p = 0.3817), and main combination X drug dose interaction (F(3,48) = 1.141; p = 0.3419), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 8.758; p < 0.0001), main effect of combination (F(1,48) = 0.326; p = 0.5707), and main combination X drug dose interaction (F(3,48) = 1.493; p = 0.2284), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 12.55; p < 0.0001), main effect of combination (F(1,48) = 1.875; p = 0.1773), and Significant main combination X drug dose interaction (F(3,48) = 4.348; p = 0.0083). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. # indicates a difference that is significant between the different rat groups. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [STZ] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 4.
Effects of intraperitoneal injections of different drug combinations on STZ-induced mechanical allodynia. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 7.855; p = 0.0002), Significant main effect of combination (F(1,48) = 8.748; p = 0.0048), and main combination X drug dose interaction (F(3,48) = 0.5447; p = 0.6541), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 13.61; p < 0.0001), main effect of combination (F(1,48) = 0.7796; p = 0.3817), and main combination X drug dose interaction (F(3,48) = 1.141; p = 0.3419), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 8.758; p < 0.0001), main effect of combination (F(1,48) = 0.326; p = 0.5707), and main combination X drug dose interaction (F(3,48) = 1.493; p = 0.2284), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on STZ-induced changes in % MPE. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,48) = 12.55; p < 0.0001), main effect of combination (F(1,48) = 1.875; p = 0.1773), and Significant main combination X drug dose interaction (F(3,48) = 4.348; p = 0.0083). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. # indicates a difference that is significant between the different rat groups. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % MPE = (PWT after drug application − PWT before drug application)/(PWT before manipulation [STZ] − PWT before drug application) × 100. PWT indicates paw withdrawal threshold in grams. Rectangular boxes indicate vehicle treatment.
Figure 5.
Effects of intraperitoneal injections of cannabinoids on locomotion. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 20.62; p < 0.0001), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts, One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 6.758; p = 0.0025), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 31.83; p < 0.0001), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 6.881; p = 0.0023), Data are expressed as mean ± SEM of % X and % Z total counts. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 5.
Effects of intraperitoneal injections of cannabinoids on locomotion. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 20.62; p < 0.0001), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts, One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 6.758; p = 0.0025), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 31.83; p < 0.0001), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 6.881; p = 0.0023), Data are expressed as mean ± SEM of % X and % Z total counts. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 6.
Effects of intraperitoneal injections of opioids on locomotion. (A) Effects of intraperitoneal injections of morphine (0.32, 1, and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 4.406; p = 0.0156), (B) Effects of intraperitoneal injections of morphine (0.32, 1, and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 2.583; p = 0.0819), (C) Effects of intraperitoneal injections of tramadol (1, 3 and 10 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 7.232; p = 0.0018), (D) Effects of intraperitoneal injections of tramadol (1, 3 and 10 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 4.972; p = 0.0097). Data are expressed as mean ± SEM of % X and % Z total counts. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 6.
Effects of intraperitoneal injections of opioids on locomotion. (A) Effects of intraperitoneal injections of morphine (0.32, 1, and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 4.406; p = 0.0156), (B) Effects of intraperitoneal injections of morphine (0.32, 1, and 3.2 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 2.583; p = 0.0819), (C) Effects of intraperitoneal injections of tramadol (1, 3 and 10 mg/kg) or vehicle (3% tween 20 in saline) on % X total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 7.232; p = 0.0018), (D) Effects of intraperitoneal injections of tramadol (1, 3 and 10 mg/kg) or vehicle (3% tween 20 in saline) on % Z total counts. One-way ANOVA revealed the following results: Significant main effect of treatment (F(3,20) = 4.972; p = 0.0097). Data are expressed as mean ± SEM of % X and % Z total counts. One-way ANOVA test was used to analyze data followed by Dunnett’s post-hoc test, * p < 0.05, n = 8 rats per group. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 7.
Effects of intraperitoneal injections of HU210 combined with morphine or tramadol on locomotion. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 13.89; p < 0.0001), main effect of combination (F(1,40) = 0.05348; p = 0.08183), and main combination X drug dose interaction (F(3,40) = 0.5588; p = 0.6553), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 5.749; p = 0.0032), main effect of combination (F(1,40) = 4.788; p = 0.0347), and main combination X drug dose interaction (F(3,40) = 0.1388; p = 0.9362) (C) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 20.48; p < 0.0001), main effect of combination (F(1,40) = 2.666; p = 0.1104), and main combination X drug dose interaction (F(3,40) = 1.001; p = 0.4023) (D) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 3.134; p = 0.0363), main effect of combination (F(1,40) = 2.674; p = 0.1101), and main combination X drug dose interaction (F(3,40) = 0.3628; p = 0.7764). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 7.
Effects of intraperitoneal injections of HU210 combined with morphine or tramadol on locomotion. (A) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 13.89; p < 0.0001), main effect of combination (F(1,40) = 0.05348; p = 0.08183), and main combination X drug dose interaction (F(3,40) = 0.5588; p = 0.6553), (B) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 5.749; p = 0.0032), main effect of combination (F(1,40) = 4.788; p = 0.0347), and main combination X drug dose interaction (F(3,40) = 0.1388; p = 0.9362) (C) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 20.48; p < 0.0001), main effect of combination (F(1,40) = 2.666; p = 0.1104), and main combination X drug dose interaction (F(3,40) = 1.001; p = 0.4023) (D) Effects of intraperitoneal injections of HU210 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 3.134; p = 0.0363), main effect of combination (F(1,40) = 2.674; p = 0.1101), and main combination X drug dose interaction (F(3,40) = 0.3628; p = 0.7764). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 8.
Effects of intraperitoneal injections of WIN55212 combined with morphine or tramadol on locomotion. (A) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 8.789; p = 0.0001), main effect of combination (F(1,40) = 0.0032; p = 0.9545), and main combination X drug dose interaction (F(3,40) = 0.1459; p = 0.9317), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 6.867; p = 0.0008), main effect of combination (F(1,40) = 0.4038; p = 0.5288), and main combination X drug dose interaction (F(3,40) = 0.8312; p = 0.4848), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 20.86; p < 0.0001), main effect of combination (F(1,40) = 2.367; p = 0.1318), and main combination X drug dose interaction (F(3,40) = 0.8829; p = 0.4582), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 9.842; p < 0.0001), main effect of combination (F(1,40) = 0.07276; p = 0.7888), and main combination X drug dose interaction (F(3,40) = 0.2696; p = 0.8469). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Figure 8.
Effects of intraperitoneal injections of WIN55212 combined with morphine or tramadol on locomotion. (A) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 8.789; p = 0.0001), main effect of combination (F(1,40) = 0.0032; p = 0.9545), and main combination X drug dose interaction (F(3,40) = 0.1459; p = 0.9317), (B) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of morphine (0.32 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 6.867; p = 0.0008), main effect of combination (F(1,40) = 0.4038; p = 0.5288), and main combination X drug dose interaction (F(3,40) = 0.8312; p = 0.4848), (C) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % X total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 20.86; p < 0.0001), main effect of combination (F(1,40) = 2.367; p = 0.1318), and main combination X drug dose interaction (F(3,40) = 0.8829; p = 0.4582), (D) Effects of intraperitoneal injections of WIN55212 (0.1, 0.32 and 1 mg/kg) plus the subtherapeutic dose of tramadol (1 mg/kg) on % Z total counts. Two-way ANOVA revealed the following results: Significant main effect of drug dose (F(3,40) = 9.842; p < 0.0001), main effect of combination (F(1,40) = 0.07276; p = 0.7888), and main combination X drug dose interaction (F(3,40) = 0.2696; p = 0.8469). Two-way ANOVA test was used to analyze data followed by Holm–Sidak post-hoc test. * indicates a difference that is significant compared with day 0 within the same rat group. Data represent mean ± SEM of 8 rats. % X total counts = (X total counts after drug application/baseline X total counts) × 100. % Z total counts = (Z total counts after drug application/baseline Z total counts) × 100. Rectangular boxes indicate vehicle treatment.
Table 1.
Latin square design showing the injection of each tested drug in days 3–9 post-CFA injection. HU210 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). WIN55212 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). Morphine (dose 1 = 0.32 mg/kg, dose 2 = 1 mg/kg and dose 3 = 3.2 mg/kg). Tramadol (dose 1 = 1 mg/kg, dose 2 = 32 mg/kg and dose 3 = 10 mg/kg).
Table 1.
Latin square design showing the injection of each tested drug in days 3–9 post-CFA injection. HU210 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). WIN55212 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). Morphine (dose 1 = 0.32 mg/kg, dose 2 = 1 mg/kg and dose 3 = 3.2 mg/kg). Tramadol (dose 1 = 1 mg/kg, dose 2 = 32 mg/kg and dose 3 = 10 mg/kg).
| Days Post-CFA Injection |
---|
Day 3 | Day 5 | Day 7 | Day 9 |
---|
Rats 1 and 2 | Vehicle | Dose 1 | Dose 2 | Dose 3 |
Rats 3 and 4 | Dose 3 | Vehicle | Dose 1 | Dose 2 |
Rats 5 and 6 | Dose 2 | Dose 3 | Vehicle | Dose 1 |
Rats 7 and 8 | Dose 1 | Dose 2 | Dose 3 | Vehicle |
Table 2.
Latin square design showing the injection of each tested drug in days 1–7 in week 4 post-streptozotocin (STZ) injection. HU210 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). WIN55212 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). Morphine (dose 1 = 0.32 mg/kg, dose 2 = 1 mg/kg and dose 3 = 3.2 mg/kg). Tramadol (dose 1 = 1 mg/kg, dose 2 = 32 mg/kg and dose 3 = 10 mg/kg).
Table 2.
Latin square design showing the injection of each tested drug in days 1–7 in week 4 post-streptozotocin (STZ) injection. HU210 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). WIN55212 (dose 1 = 0.1 mg/kg, dose 2 = 0.32 mg/kg and dose 3 = 1 mg/kg). Morphine (dose 1 = 0.32 mg/kg, dose 2 = 1 mg/kg and dose 3 = 3.2 mg/kg). Tramadol (dose 1 = 1 mg/kg, dose 2 = 32 mg/kg and dose 3 = 10 mg/kg).
| Days in Week 4 Post-STZ Injection |
---|
Day 1 | Day 3 | Day 5 | Day 7 |
---|
Rats 1 and 2 | Vehicle | Dose 1 | Dose 2 | Dose 3 |
Rats 3 and 4 | Dose 3 | Vehicle | Dose 1 | Dose 2 |
Rats 5 and 6 | Dose 2 | Dose 3 | Vehicle | Dose 1 |
Rats 7 and 8 | Dose 1 | Dose 2 | Dose 3 | Vehicle |