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The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain

Item Type:Article
Title:The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain
Creators Name:Hartmann, B. and Ahmadi, S. and Heppenstall, P.A. and Lewin, G.R. and Schott, C. and Borchardt, T. and Seeburg, P.H. and Zeilhofer, H.U. and Sprengel, R. and Kuner, R.
Abstract:Ca2+-permeable AMPA receptors are densely expressed in the spinal dorsal horn, but their functional significance in pain processing is not understood. By disrupting the genes encoding GluR-A or GluR-B, we generated mice exhibiting increased or decreased numbers of Ca2+-permeable AMPA receptors, respectively. Here, we demonstrate that AMPA receptors are critical determinants of nociceptive plasticity and inflammatory pain. A reduction in the number of Ca2+-permeable AMPA receptors and density of AMPA channel currents in spinal neurons of GluR-A-deficient mice is accompanied by a loss of nociceptive plasticity in vitro and a reduction in acute inflammatory hyperalgesia in vivo. In contrast, an increase in spinal Ca2+- permeable AMPA receptors in GluR-B-deficient mice facilitated nociceptive plasticity and enhanced long-lasting inflammatory hyperalgesia. Thus, AMPA receptors are not mere determinants of fast synaptic transmission underlying basal pain sensitivity as previously thought, but are critically involved in activity-dependent changes in synaptic processing of nociceptive inputs.
Keywords:AMPA Receptors, Brain, Excitatory Postsynaptic Potentials, Immunohistochemistry, Inflammation, Knockout Mice, Neural Pathways, Neuronal Plasticity, Nociceptors, Organ Culture Techniques, Pain, Spinal Cord, Animals, Mice
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press
Volume:44
Number:4
Page Range:637-650
Date:18 November 2004
Official Publication:https://doi.org/10.1016/j.neuron.2004.10.029
PubMed:View item in PubMed

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