Cold hypersensitivity after administration of oxaliplatin to mice. (A) Cold hypersensitivity was assessed by counting forepaw and hind paw shakes of mice placed on a cold plate set at 15°C during 150-s testing periods (15°C-cold plate test). Assessments were made before and 1, 2, 3, 4, 5, 7, 9, and 12 days after a single injection of oxaliplatin (2, 5, or 15 mg/kg) or vehicle (n = 6 for each group). (B) Temperature preference was assessed by the two-plate temperature preference test. Mice were placed in a chamber containing two identical, adjacent floor platforms with one set to a fixed temperature of 24°C and the other (test plate) set to 24°, 20°, 15°, 5°, or 0°C. The time spent on the test plate during a 10-min testing period was measured. Testing was performed before any drug administration and 4 days after administration of oxaliplatin (15 mg/kg) or vehicle (n = 10 for each group). (C) Cold hypersensitivity was also assessed by the 15°C-cold plate test 4 days after each of the three weekly administrations of oxaliplatin (each dose at 15 mg/kg; n = 10 for each group). Data were given as the mean ± SEM and analyzed by two-way ANOVA for repeated measures in (A) and (C) and by two-way ANOVA in (B) followed by Bonferroni multiple comparison tests (A, group effect: P < 0.001; time effect: P < 0.001; B, group effect: P < 0.001; temperature effect: P < 0.001; C, group effect: P < 0.001; time effect: P < 0.001). * P < 0.05, ** P < 0.01, *** P < 0.001 vs. corresponding time point of control group (A). OHP = oxaliplatin; VEH = vehicle.