Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Transport System X-AG / drug effects
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Amino Acid Transport System X-AG / metabolism*
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Animals
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Antineoplastic Agents, Phytogenic
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Cell Communication / drug effects
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Cell Communication / physiology
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2 / drug effects
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Excitatory Amino Acid Transporter 2 / metabolism*
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Glutamate Plasma Membrane Transport Proteins
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Glutamic Acid / metabolism
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Hyperalgesia / chemically induced
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Hyperalgesia / metabolism*
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Hyperalgesia / physiopathology
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Male
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Neuroglia / drug effects
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Neuroglia / metabolism
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Nociceptors / drug effects
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Nociceptors / metabolism
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Paclitaxel*
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Peripheral Nervous System Diseases / chemically induced
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Peripheral Nervous System Diseases / metabolism*
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Peripheral Nervous System Diseases / physiopathology
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Posterior Horn Cells / drug effects
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Posterior Horn Cells / metabolism*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Rats
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Rats, Sprague-Dawley
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Symporters / drug effects
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Symporters / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Amino Acid Transport System X-AG
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Antineoplastic Agents, Phytogenic
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2
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Glutamate Plasma Membrane Transport Proteins
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Slc1a3 protein, rat
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Symporters
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Glutamic Acid
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Paclitaxel