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

Abstract

Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-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.

• Authors: Bettina Hartmann, Seifollah Ahmadi, Paul A Heppenstall, Gary R Lewin, Claus Schott, Thilo Borchardt, Peter H Seeburg, Hanns Ulrich Zeilhofer, Rolf Sprengel, Rohini Kuner
• Journal: Neuron (Neuron) Vol. 44 Issue 4 Pg. 637-50 (Nov 18 2004) ISSN: 0896-6273 [Print] United States
• PMID: 15541312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, AMPA
• glutamate receptor type B
• glutamate receptor ionotropic, AMPA 1

Topics

• Animals
• Brain (physiology)
• Excitatory Postsynaptic Potentials
• Female
• Immunohistochemistry
• Inflammation (etiology, physiopathology)
• Male
• Mice
• Mice, Knockout
• Neural Pathways (physiology)
• Neuronal Plasticity (physiology)
• Nociceptors (physiology)
• Organ Culture Techniques
• Pain (complications, physiopathology)
• Receptors, AMPA (deficiency, genetics)
• Spinal Cord (physiology)