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GlyR 3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization
Robert J. Harvey,1,8*Ulrike B. Depner,2*Heinz Wässle,3Seifollah Ahmadi,2Cornelia Heindl,2Heiko Reinold,2Trevor G. Smart,4Kirsten Harvey,1Burkhard Schütz,5Osama M. Abo-Salem,5Andreas Zimmer,5Pierrick Poisbeau,6Hans Welzl,7David P. Wolfer,7Heinrich Betz,8Hanns Ulrich Zeilhofer,2Ulrike Müller8
Prostaglandin E2 (PGE2) is a crucial mediator of inflammatorypain sensitization. Here, we demonstrate that inhibition ofa specific glycine receptor subtype (GlyR 3) by PGE2-inducedreceptor phosphorylation underlies central inflammatory painsensitization. We show that GlyR 3 is distinctly expressed insuperficial layers of the spinal cord dorsal horn. Mice deficientin GlyR 3 not only lack the inhibition of glycinergic neurotransmissionby PGE2 seen in wild-type mice but also show a reduction inpain sensitization induced by spinal PGE2 injection or peripheralinflammation. Thus, GlyR 3 may provide a previously unrecognizedmolecular target in pain therapy.
1 Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK. 2 Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany. 3 Abteilung Neuroanatomie, Max-Planck-Institut für Hirnforschung, D-60528 Frankfurt, Germany. 4 Department of Pharmacology, University College London, London WC1E 6BT, UK. 5 Institut für Molekulare Neurobiologie, Universitätsklinikum Bonn, D-53105 Bonn, Germany. 6 Laboratoire de Neurophysiologie Cellulaire et Intégrée, Université Louis Pasteur/CNRS UMR 7519, 67084 Strasbourg, France. 7 Abteilung für Neuroanatomie und Verhalten, Institut für Anatomie, Universität Zürich–Irchel, CH-8057 Zürich, Switzerland. 8 Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, D-60528 Frankfurt, Germany.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: umueller{at}mpih-frankfurt.mpg.de (U.M.); neurochemie{at}mpih-frankfurt.mpg.de (H.B.)
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3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization
3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR 
To whom correspondence should be addressed. E-mail: 
