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Translocation of GluR1-containing AMPA receptors to a spinal nociceptive synapse during acute noxious stimulation.

Larsson, Max LU and Broman, Jonas LU (2008) In The Journal of neuroscience : the official journal of the Society for Neuroscience 28(28). p.7084-7090
Abstract
Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or tissue injury. However, the specific synaptic populations that may be subject to such plasticity have not been identified. Using neuronal tracing and postembedding immunogold labeling, we show that a model of acute inflammatory hyperalgesia is associated with an elevated density of GluR1-containing AMPA receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits, at synapses established by C-fibers that lack the... (More)
Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or tissue injury. However, the specific synaptic populations that may be subject to such plasticity have not been identified. Using neuronal tracing and postembedding immunogold labeling, we show that a model of acute inflammatory hyperalgesia is associated with an elevated density of GluR1-containing AMPA receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits, at synapses established by C-fibers that lack the neuropeptide substance P. A more subtle increase in GluR1 immunolabeling was noted at synapses formed by substance P-containing nociceptors. No changes in either GluR1 or GluR2/3 contents were observed at synapses formed by low-threshold mechanosensitive primary afferent fibers. These results contrast with our previous observations in the same pain model of increased and decreased levels of activated CaMKII at synapses formed by peptidergic and nonpeptidergic nociceptive fibers, respectively, suggesting that the observed redistribution of AMPA receptor subunits does not depend on postsynaptic CaMKII activity. The present ultrastructural evidence of topographically specific, activity-dependent insertion of GluR1-containing AMPA receptors at a central synapse suggests that potentiation of nonpeptidergic C-fiber synapses by this mechanism contributes to inflammatory pain. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
28
issue
28
pages
7084 - 7090
publisher
Society for Neuroscience
external identifiers
  • WOS:000257472000009
  • PMID:18614677
  • Scopus:49049102134
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.5749-07.2008
language
English
LU publication?
yes
id
f95f2a55-d571-47c1-9e29-a204962407a2 (old id 1181333)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18614677?dopt=Abstract
date added to LUP
2008-08-07 13:53:06
date last changed
2016-11-13 04:26:55
@misc{f95f2a55-d571-47c1-9e29-a204962407a2,
  abstract     = {Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or tissue injury. However, the specific synaptic populations that may be subject to such plasticity have not been identified. Using neuronal tracing and postembedding immunogold labeling, we show that a model of acute inflammatory hyperalgesia is associated with an elevated density of GluR1-containing AMPA receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits, at synapses established by C-fibers that lack the neuropeptide substance P. A more subtle increase in GluR1 immunolabeling was noted at synapses formed by substance P-containing nociceptors. No changes in either GluR1 or GluR2/3 contents were observed at synapses formed by low-threshold mechanosensitive primary afferent fibers. These results contrast with our previous observations in the same pain model of increased and decreased levels of activated CaMKII at synapses formed by peptidergic and nonpeptidergic nociceptive fibers, respectively, suggesting that the observed redistribution of AMPA receptor subunits does not depend on postsynaptic CaMKII activity. The present ultrastructural evidence of topographically specific, activity-dependent insertion of GluR1-containing AMPA receptors at a central synapse suggests that potentiation of nonpeptidergic C-fiber synapses by this mechanism contributes to inflammatory pain.},
  author       = {Larsson, Max and Broman, Jonas},
  issn         = {1529-2401},
  language     = {eng},
  number       = {28},
  pages        = {7084--7090},
  publisher    = {ARRAY(0x969a510)},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Translocation of GluR1-containing AMPA receptors to a spinal nociceptive synapse during acute noxious stimulation.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.5749-07.2008},
  volume       = {28},
  year         = {2008},
}