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.
|Titolo:||The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain|
|Autori:||Hartmann, Bettina; Ahmadi, Seifollah; Heppenstall, Paul A.; Lewin, Gary R.; Schott, Claus; Borchardt, Thilo; Seeburg, Peter H.; Zeilhofer, Hanns Ulrich; Sprengel, Rolf; Kuner, Rohini|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||10.1016/j.neuron.2004.10.029|
|Appare nelle tipologie:||1.1 Journal article|