Figure 1.

Time-dependent symmetric decrease in mechanical nociceptive threshold produced by oxaliplatin, paclitaxel and bortezomib. Oxaliplatin [2 mg/kg, intravenously (i.v.), on Day 0], paclitaxel [1 mg/kg, intraperitoneally (i.p.), on Days 0, 2, 4 and 6] or bortezomib (0.2 mg/kg, i.v., on Days 0, 2, 4 and 6) were administered to groups of male rats, and the magnitude of hyperalgesia was measured over 28 days. Top: Oxaliplatin decreased the nociceptive threshold from the first time point (30 min), and it remained undiminished over the 28-day testing period. For paclitaxel and bortezomib, the time-dependent decrease in the nociceptive threshold reached a maximum on Day 7 and remained undiminished for the rest of the 28-day testing period. Bottom: A symmetry index was calculated at every time point, as the absolute (unsigned) value of the difference between the reduction in nociceptive threshold in the right minus left paws, for each rat, expressed as a percentage of the baseline nociceptive threshold. There was no time dependence of the symmetry index for any of the three agents tested, and the average levels remained very low at all time points (mean values: oxaliplatin 4.4%, paclitaxel 6.0% and bortezomib 3.3%), supporting the presence of symmetry in hind paw mechanical hyperalgesia throughout the time course of the study (Days 0–28) for all three chemotherapy drugs. Values are presented as mean ± SEM; n = 12 for oxaliplatin- and paclitaxel-, and n = 8 for bortezomib-treated rats.