Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia.
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.
Cata
J P
JP
Department of Anesthesiology and Pain Research, Division of Anesthesiology and Critical Care Medicine, University of Texas-M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Weng
H-R
HR
Chen
J-H
JH
Dougherty
P M
PM
D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D001522:Behavior, Animal / Q000187:drug effects; D003627:Data Interpretation, Statistical; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017239:Paclitaxel; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D027322:Amino Acid Transport System X-AG; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel