Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat.
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.
Vikman
Kristina S
KS
Pain Management Research Institute, Kolling Institute, The University of Sydney at Royal North Shore Hospital, St Leonards NSW 2065, Australia.
Rycroft
Beth K
BK
Christie
Macdonald J
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D008297:Male; D009431:Neural Conduction / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D000094942:Nociceptin Receptor
D002118:Calcium; D005620:Freund's Adjuvant; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C121001:NR2B NMDA receptor; C000722285:Oprl1 protein, rat