Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia.
Changes in the expression of glial glutamate transporters (GLAST and GLT-1) were examined in the spinal cord of rats with chemotherapy (taxol)-induced mechanical hyperalgesia. Immunohistochemical studies show that the expression of both GLAST and GLT-1 in the L4-L5 spinal dorsal horn is decreased by 24% (P<0.001) and 23% (P<0.001), respectively, in rats with taxol-induced hyperalgesia as compared with those in control rats. These changes were further confirmed using an enzyme-linked immunosorbent assay that confirmed downregulation of GLAST by 36% (P<0.05) and GLT-1 by 18% (P<0.05) in the L4-L5 spinal cord of taxol-treated rats. These data indicate that downregulation of glutamate transporters may contribute to the development of hyperalgesia induced by taxol and suggest that glutamate transporters may be a new target for treatment of pain.
Department of Anesthesiology and Pain Medicine, Division of Anesthesiology and Critical Care, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd #42, Houston, TX 77030, USA. hrweng@mdanderson.org
Han-Rong
HR
Weng
Natarajan
N
Aravindan
Juan P
JP
Cata
Jing-Hong
JH
Chen
Andrew D S
AD
Shaw
Patrick M
PM
Dougherty
D027322:Amino Acid Transport System X-AG / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000187:drug effects / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D027322:Amino Acid Transport System X-AG; D000972:Antineoplastic Agents, Phytogenic; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493392:Slc1a3 protein, rat; D027981:Symporters; D018698:Glutamic Acid; D017239:Paclitaxel