Is required for paclitaxel to induce acute pain in rodents. The direct impacts induced by paclitaxel on the spinal glutamatergic synapses and glial glutamate transporters were uncovered.ResultsIntravenous injection of paclitaxel induces acute pain in rodentsintravenous (i.v.) administration of taxol used in the clinic. Vehicle control (1 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27788604 ml) was injected into the rats in the same fashion in the control group. A single i.v. injection of taxol reduced thresholds of hind paw withdrawal responses to mechanical stimuli, which occurred within 2 hrs and peaked at 4 hrs but resolved within 24 hrs after taxol injection (Figure 1A). Meanwhile, thresholds of hind paw withdrawal responses to mechanical stimuli in rats receiving vehicle (control group) remained unchanged. This is in agreement with a previous report [32] showing that a single intraperitoneal injection (i.p.) of paclitaxel (1 mg/kg) in rats induces acute mechanical allodynia between 1 and 6 hrs after paclitaxel treatment. Furthermore, we also determined the changes of mechanical thresholds following i.v. paclitaxel injection at a higher dose (5 mg/kg). Mechanical allodynia was observed within 1 hr, peaked between 4 to 6 hrs, lasted more than 48 hrs, and ended before 72 hrs after paclitaxel injection (Figure 1B), which lasts significantly longer than that induced by paclitaxel at 2 mg/kg (Figure 1A). At the same time period, mechanical thresholds in rats receiving vehicle were not significantly altered. These data indicate that paclitaxel induces acute mechanical allodynia in a dose-dependent manner. Recent studies have demonstrated that innate burrowing behavior can be used to measure the wellbeing of rodents. When animals are in a status of pain, burrowing behavior is reduced [33,34]. We then measured burrowing behaviors in rats treated with paclitaxel. After quantifying the burrowing behavior at baseline, rats were divided into two groups, one group receiving i.v. paclitaxel, the other receiving vehicle. We first determined burrowing behaviors in rats receiving i.v. paclitaxel (2 mg/kg) or vehicle. As mechanical allodynia induced by paclitaxel at this dose peaked at 4 hrs and disappeared at PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26713783 24 hrs after paclitaxel injection, burrowing behaviors were measured at 4 and 24 hrs after the i.v. injection. In comparison with their own baseline and their counterpart in the vehicle group, the burrowing behaviors in the paclitaxel group were significantly decreased at 4 hrs, but returned to baseline by 24 hrs (Figure 1C). When we measured burrowing behaviors in rats receiving paclitaxel at 5 mg/kg (i.v.), we found that burrowing behaviors were significantly reduced at 4, 24, and 48 hrs, but recovered by 72 hrs after paclitaxel injection (Figure 1D). Taking all data in Figure 1 together, we conclude that paclitaxel induces acute pain in rats in a dose-dependent manner.Low levels of paclitaxel are found in the CSF and spinal dorsal horn after paclitaxel injection and intrathecal injection of paclitaxel induces acute pain in ratsTo determine whether paclitaxel induces acute pain in animals, nociceptive behaviors in rats were examined after the rats were treated with paclitaxel or saline. Paclitaxel (dose: 2 mg/kg; volume: 1 ml; duration of the injection: 1 min) was given to rats via the tail vein to simulateTo investigate whether paclitaxel penetration into the spinal dorsal horn correlates to paclitaxel-induced acute PluriSIn 1 pain, paclitaxel concentrations in the CSF and spinalYan et al. Molecular Pain.
