The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes kawamoto is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain.
In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats.
Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2—21 days after the infusion. Transgene expression was primarily localized to astrocytes.
Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were mobile porn videi 7 or 14 days after the nerve ligation.
These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation.
Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. The spinal glutamatergic system plays a key role in normal pain transmission and in the induction of central sensitization, the neuronal plasticity underlying pathological pain at the spinal tastymom. Glutamate release in the spinal dorsal horn is elicited following peripheral inflammation or nerve injury [ 1 - 5 kawamoto.
This removal maintains the extracellular glutamate concentration in the physiological range, preventing the glutamate overexcitation and neurotoxicity that can occur under a variety of pathological conditions and modulating kawamoto neuronal plasticity [ 9 - 11 ]. Among these five subtypes, GLT-1 enriched in astrocytic processes appears to be the most abundant EAAT and may represent the predominant route for clearance of kawamoto glutamate in the spinal cord [ 11 ].
Furthermore, astrocytes are able to specifically metabolize incorporated glutamate into glutamine with the enzyme glutamine synthetase [ 10 ].
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