Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia

Neuroscience. 2006;138(1):329-38. doi: 10.1016/j.neuroscience.2005.11.009. Epub 2005 Dec 19.


Changes in the signaling of wide dynamic range neurons and the expression of glutamate transporters in the lumbar spinal dorsal horn of rats with Taxol-induced hyperalgesia are detailed in this report. Deep spinal lamina neurons have significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli, increased responses to both skin heating and cooling, and increased after-discharges and abnormal windup to transcutaneous electrical stimuli. The expression of glutamate transporter proteins in the dorsal horn is decreased at the time point corresponding to the physiological changes. These results suggest a state of increased excitability develops in spinal pain-signaling neurons as a consequence of decreased glutamate clearance. These changes in dorsal horn neurobiology likely in turn contribute to the hyper-responsiveness to sensory stimuli seen in animals treated with Taxol and may play a role in the pain seen in cancer patients receiving Taxol.

MeSH terms

  • Amino Acid Transport System X-AG / biosynthesis*
  • Amino Acid Transport System X-AG / genetics
  • Animals
  • Antineoplastic Agents, Phytogenic*
  • Behavior, Animal / drug effects
  • Data Interpretation, Statistical
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Electric Stimulation
  • Electrophysiology
  • Evoked Potentials / drug effects
  • Hot Temperature
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Immunohistochemistry
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Paclitaxel*
  • Pain Measurement / drug effects
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / pathology
  • Physical Stimulation
  • Posterior Horn Cells / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology*


  • Amino Acid Transport System X-AG
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel