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J Physiol Volume 586, Number 2, 515-527, January 15, 2008 DOI: 10.1113/jphysiol.2007.145581
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NEUROSCIENCE

Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat

 Kristina S. Vikman1, Beth K. Rycroft1 and Macdonald J. Christie1

1 Pain Management Research Institute, Kolling Institute, The University of Sydney at Royal North Shore Hospital, St Leonards NSW 2065, Australia

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 Ca2+-permeable AMPAR channel blocker 1-naphthylacetyl spermine (NAS) was also observed, indicating an increase in the contribution of Ca2+-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 Mg2+ sensitivity suggests a down regulation of the highly Mg2+-sensitive and high conductance NR2B subunit at this synapse. These changes in glutamatergic receptor function during inflammation support the selective effectiveness of Ca2+-permeable AMPAR antagonists in inflammatory pain models and may underlie the reported ineffectiveness of NR2B antagonists in spinal antinociception.

(Received 28 September 2007; accepted after revision 12 November 2007; first published online 22 November 2007)
Corresponding author M. J. Christie: Pain Management, University of Sydney at Royal North Shore Hospital, St Leonards 2065 Australia. Email: macc{at}med.usyd.edu.au

K. S. Vikman and B. K. Rycroft contributed equally to this work.






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