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Switch to Ca 2+ ‐permeable AMPA and reduced NR2B NMDA receptor‐mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat
Author(s) -
Vikman Kristina S.,
Rycroft Beth K.,
Christie Macdonald J.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.145581
Subject(s) - ampa receptor , nmda receptor , neurotransmission , glutamate receptor , synapse , chemistry , nociception , neuroscience , glutamatergic , excitatory postsynaptic potential , pharmacology , biophysics , receptor , medicine , biology , biochemistry
Glutamate receptor response properties of nociceptive synapses on neurokinin 1 receptor positive (NK1R + ) lamina I neurons were determined 3 days after induction of chronic peripheral inflammation with Freund's Complete Adjuvant (CFA). A significant increase in the AMPAR/NMDAR ratio was found during inflammation, which was associated with a significant reduction in the quantal amplitude of NMDAR‐mediated synaptic currents. A significant shortening of the quantal AMPA current decay, a greater inward rectification of the AMPAR‐mediated eEPSC amplitude and an increased sensitivity to the Ca 2+ ‐permeable AMPAR channel blocker 1‐naphthylacetyl spermine (NAS) was also observed, indicating an increase in the contribution of Ca 2+ ‐permeable AMPARs at this synapse during inflammation. Furthermore the reduced effectiveness of the NR2B‐specific antagonist CP‐101,606 on NMDAR‐mediated eEPSCs together with a decrease in Mg 2+ sensitivity suggests a down regulation of the highly Mg 2+ ‐sensitive and high conductance NR2B subunit at this synapse. These changes in glutamatergic receptor function during inflammation support the selective effectiveness of Ca 2+ ‐permeable AMPAR antagonists in inflammatory pain models and may underlie the reported ineffectiveness of NR2B antagonists in spinal antinociception.