Abstract
Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca2+/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.
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Dates
Type | When |
---|---|
Created | 17 years, 1 month ago (July 9, 2008, 12:23 p.m.) |
Deposited | 2 years, 4 months ago (April 13, 2023, 2:45 p.m.) |
Indexed | 3 months, 2 weeks ago (May 20, 2025, 8:11 a.m.) |
Issued | 17 years, 1 month ago (July 9, 2008) |
Published | 17 years, 1 month ago (July 9, 2008) |
Published Online | 17 years, 1 month ago (July 9, 2008) |
Published Print | 17 years, 1 month ago (July 9, 2008) |
@article{Larsson_2008, title={Translocation of GluR1-Containing AMPA Receptors to a Spinal Nociceptive Synapse during Acute Noxious Stimulation}, volume={28}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.5749-07.2008}, DOI={10.1523/jneurosci.5749-07.2008}, number={28}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Larsson, Max and Broman, Jonas}, year={2008}, month=jul, pages={7084–7090} }