QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 11, 2009, 29(10):3206-3219; doi:10.1523/JNEUROSCI.4514-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Park, J.-S. Articles by Tao, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Park, J.-S. Articles by Tao, Y.-X.

 Previous Article  |  Next Article 

Neurobiology of Disease
Persistent Inflammation Induces GluR2 Internalization via NMDA Receptor-Triggered PKC Activation in Dorsal Horn Neurons

Jang-Su Park,^1 * Nana Voitenko,^2 * Ronald S. Petralia,³ Xiaowei Guan,¹ Ji-Tian Xu,¹ Jordan P. Steinberg,⁴ Kogo Takamiya,^4,5 Andrij Sotnik,² Olga Kopach,² Richard L. Huganir,^4,6 and Yuan-Xiang Tao¹

¹Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, ²Department of General Physiology of Nervous System, Bogomoletz Institute of Physiology, Kiev 01024, Ukraine, ³Laboratory of Neurochemistry, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, and Departments of ⁴Neuroscience and ⁵Neurosurgery and ⁶Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Correspondence should be addressed to Dr. Yuan-Xiang Tao, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 367 Ross, 720 Rutland Avenue, Baltimore, MD 21205. Email: ytao1{at}jhmi.edu

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.

---

Received Sept. 20, 2008; revised Feb. 4, 2009; accepted Feb. 9, 2009.

Correspondence should be addressed to Dr. Yuan-Xiang Tao, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 367 Ross, 720 Rutland Avenue, Baltimore, MD 21205. Email: ytao1{at}jhmi.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help