Paclitaxel-induced hyperalgesia modulates negative affective component of pain and NR1 receptor expression in the frontal cortex in rats

Neurosci Res. 2014 Mar;80:32-7. doi: 10.1016/j.neures.2014.01.002. Epub 2014 Jan 17.


Paclitaxel, one of the chemotherapeutic agents clinically used to treat several types of cancer, produces side effects such as peripheral neuropathy, sensory abnormalities, and hyperalgesia. Since hyperalgesia remains after cessation of paclitaxel therapy and becomes chronic, we hypothesize that alteration in memory and the cognitive process of pain underlies hyperalgesia. To test this hypothesis, we examined whether drug-induced hyperalgesia alters the affective component of pain and the NMDA-NR1 and mGluR1 receptors as a mediator for signal transmission and memory of pain. Mechanical sensitivity was measured by von Frey filament test after intraperitoneal injection of paclitaxel in rats. Paclitaxel-induced hyperalgesia was confirmed over almost the entire 14-day period of observation after the treatment. The effect of paclitaxel-induced hyperalgesia on the affective component of pain was assessed using pain-induced place aversion. The formalin-induced conditioned place aversion was completely abolished in the paclitaxel-treated rats. Immunoblot analysis of NR1 and mGluR1 protein levels in various brain regions was performed after paclitaxel treatment. Treatment reduced only the NR1 expression within the frontal cortex. These results suggest that the hypofunction of memory processes with the reduced NMDA receptors in the frontal cortex might be involved in the expression of abnormal emotional behaviors accompanied by hyperalgesia.

Keywords: Conditioned place aversion; Emotion; Hyperalgesia; NR1 receptor; Paclitaxel.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Conditioning, Operant / drug effects
  • Formaldehyde / adverse effects
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Hot Temperature / adverse effects
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / pathology*
  • Male
  • Nociception / drug effects
  • Nociception / physiology
  • Paclitaxel / toxicity*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Antineoplastic Agents, Phytogenic
  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Formaldehyde
  • Paclitaxel