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Science 7 May 2004:
Vol. 304. no. 5672, pp. 884 - 887
DOI: 10.1126/science.1094925
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Reports

GlyR {alpha}3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization

Robert J. Harvey,1,8* Ulrike B. Depner,2* Heinz Wässle,3 Seifollah Ahmadi,2 Cornelia Heindl,2 Heiko Reinold,2 Trevor G. Smart,4 Kirsten Harvey,1 Burkhard Schütz,5 Osama M. Abo-Salem,5 Andreas Zimmer,5 Pierrick Poisbeau,6 Hans Welzl,7 David P. Wolfer,7 Heinrich Betz,8{dagger} Hanns Ulrich Zeilhofer,2 Ulrike Müller8{dagger}

Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR {alpha}3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR {alpha}3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR {alpha}3 not only lack the inhibition of glycinergic neurotransmission by PGE2 seen in wild-type mice but also show a reduction in pain sensitization induced by spinal PGE2 injection or peripheral inflammation. Thus, GlyR {alpha}3 may provide a previously unrecognized molecular 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.

{dagger} 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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