%0 Journal Article %A Jang-Su Park %A Nana Voitenko %A Ronald S. Petralia %A Xiaowei Guan %A Ji-Tian Xu %A Jordan P. Steinberg %A Kogo Takamiya %A Andrij Sotnik %A Olga Kopach %A Richard L. Huganir %A Yuan-Xiang Tao %T Persistent Inflammation Induces GluR2 Internalization via NMDA Receptor-Triggered PKC Activation in Dorsal Horn Neurons %D 2009 %R 10.1523/JNEUROSCI.4514-08.2009 %J The Journal of Neuroscience %P 3206-3219 %V 29 %N 10 %X Spinal cord GluR2-lacking AMPA receptors (AMPARs) contribute to nociceptive hypersensitivity in persistent pain, but the molecular mechanisms underlying this event are not completely understood. We report that complete Freund's adjuvant (CFA)-induced peripheral inflammation induces synaptic GluR2 internalization in dorsal horn neurons during the maintenance of CFA-evoked nociceptive hypersensitivity. This internalization is initiated by GluR2 phosphorylation at Ser880 and subsequent disruption of GluR2 binding to its synaptic anchoring protein (GRIP), resulting in a switch of GluR2-containing AMPARs to GluR2-lacking AMPARs and an increase of AMPAR Ca2+ permeability at the synapses in dorsal horn neurons. Spinal cord NMDA receptor-mediated triggering of protein kinase C (PKC) activation is required for the induction and maintenance of CFA-induced dorsal horn GluR2 internalization. Moreover, preventing CFA-induced spinal GluR2 internalization through targeted mutation of the GluR2 PKC phosphorylation site impairs CFA-evoked nociceptive hypersensitivity during the maintenance period. These results suggest that dorsal horn GluR2 internalization might participate in the maintenance of NMDA receptor/PKC-dependent nociceptive hypersensitivity in persistent inflammatory pain. %U https://www.jneurosci.org/content/jneuro/29/10/3206.full.pdf