title: 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.affiliation: Institute for Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartmann
authors.forename: Seifollah
authors.initials: S
authors.lastname: Ahmadi
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
authors.forename: Claus
authors.initials: C
authors.lastname: Schott
authors.forename: Thilo
authors.initials: T
authors.lastname: Borchardt
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
mesh_terms: 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*
chemical_list: D018091:Receptors, AMPA; C115953:glutamate receptor type B