The glutamate transporter GLAST is involved in spinal nociceptive processing.
GLAST and GLT-1 are the most abundant glutamate transporters in the CNS and protect neurons from glutamate neurotoxicity. Here, we investigated the role of GLAST in spinal nociceptive processing. GLAST protein expression was not altered after treatment of rats with either formalin or zymosan. Surprisingly, knock-down of GLAST in the spinal cord using antisense-oligonucleotides decreased glutamate concentrations in cerebrospinal fluid (CSF) and reduced the nociceptive behaviour in the rat formalin assay. However, it did not influence thermal hyperalgesia in the zymosan-induced paw inflammation model indicating that GLAST is associated with spontaneous rather than inflammatory nociception. Mechanisms that might explain the decreased response in the formalin assay may include compensatory activation of other glutamate transporters, inhibition of glutamate release or disturbance of glutamate recycling. In conclusion, these data suggest that inhibition of GLAST expression in the spinal cord reduces excitatory synaptic activity and thereby spontaneous responses after nociceptive stimulation of the paw.
Niederberger
Ellen
E
pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, Frankfurt am Main, Germany. e.niederberger@em.uni-frankfurt.de
Schmidtko
Achim
A
Coste
Ovidiu
O
Marian
Claudiu
C
Ehnert
Corina
C
Geisslinger
Gerd
G
D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005557:Formaldehyde / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission; D015054:Zymosan / Q000494:pharmacology
D027322:Amino Acid Transport System X-AG; D016376:Oligonucleotides, Antisense; D005557:Formaldehyde; D018698:Glutamic Acid; D015054:Zymosan