The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain.
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.
Hartmann
Bettina
B
Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Ahmadi
Seifollah
S
Heppenstall
Paul A
PA
Lewin
Gary R
GR
Schott
Claus
C
Borchardt
Thilo
T
Seeburg
Peter H
PH
Zeilhofer
Hanns Ulrich
HU
Sprengel
Rolf
R
Kuner
Rohini
R
D000818:Animals; D001921:Brain / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D009924:Organ Culture Techniques; D010146:Pain / Q000150:complications / Q000503:physiopathology*; D018091:Receptors, AMPA / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000502:physiology*
D018091:Receptors, AMPA; C115953:glutamate receptor type B