The mixed CB1/CB2 agonist WIN55,212-2 and the CB2-preferring agonist AM1710 suppressed development of paclitaxel-induced mechanical and cold allodynia without significantly altering body weight. a. WIN55,212-2 (0.1 mg/kg/day s.c.) increased whereas b. AM1710 did not alter body weight in paclitaxel-treated animals. Mechanical and cold allodynia were suppressed by WIN55,212-2 (0.1 and 0.5 mg/kg/day s.c.; c. and e., respectively) and AM1710 (0.032 and 3.2 mg/kg/day s.c.; d. and f., respectively). *P < 0.05, **P <0.01, ***P <0.001 vs. Cremophor-Vehicle, #P < 0.05, ##P < 0.01, ###P <0.001 vs. Taxol-Vehicle, xP < 0.05 vs. Taxol-Agonist (high dose), +P < 0.05, ++P < 0.01 vs. Taxol-Agonist (middle dose), $P < 0.05, vs. Taxol-Agonist (low dose), βP < 0.05, ββP < 0.01, βββP < 0.001 Taxol-Agonist (middle and low doses) vs. Taxol-Vehicle,⟂⟂P < 0.01, ⟂⟂⟂P < 0.001 Taxol-Agonist (high and low doses) vs. Taxol-Vehicle, αP < 0.05 Taxol-Agonist (all doses) vs. Taxol-Vehicle, ϕϕϕP <0.001 vs. Taxol-Agonist (middle and low doses). The first drug listed indicates assignment to cremophor or paclitaxel (Taxol) treatment. The second drug indicates drug administered via osmotic mini pump chronic infusion. Day numbers reference days post-chemotherapeutic treatment (i.e., negative days indicate days prior to chemotherapeutic treatment). Surgery indicates the day (day -6) on which osmotic mini pumps were implanted subcutaneously. (ANOVA; Dunnett and Tukey post-hoc tests). N = 8–18 per group.
Rahn et al. Molecular Pain 2014 10:27 doi:10.1186/1744-8069-10-27