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

被引:78
作者
Vikman, Kristina S. [1 ]
Rycroft, Beth K. [1 ]
Christie, Macdonald J. [1 ]
机构
[1] Univ Sydney, Royal N Shore Hosp, Pain Management Res Inst, Kolling Inst, St Leonards, NSW 2065, Australia
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2008年 / 586卷 / 02期
关键词
D O I
10.1113/jphysiol.2007.145581
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glutamate receptor response properties of nociceptive synapses on neurokinin I 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.
引用
收藏
页码:515 / 527
页数:13
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