Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat.
|
| Abstract |
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.
|
|---|---|
| Authors | Kristina S Vikman, Beth K Rycroft, Macdonald J Christie |
| Journal | The Journal of physiology (J Physiol) Vol. 586 Issue 2 Pg. 515-27 (Jan 15 2008) ISSN: 0022-3751 [Print] England |
| PMID | 18033811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!