GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization
Robert J. Harvey
(1, 2)
,
Ulrike B. Depner
(3)
,
Heinz Wässle
(1)
,
Seifollah Ahmadi
(3)
,
Cornelia Heindle
(3)
,
Heiko Reinold
(3)
,
Trevor G Smart
(2)
,
Kirsten Harvey
(2)
,
Burkhard Schütz
(4)
,
Osama Abo-Salem
(4)
,
Andreas Zimmer
(4)
,
Pierrick Poisbeau
(5)
,
Hans Welzl
(6)
,
David P. Wolfer
(6)
,
Heinrich Betz
(1)
,
Hanns Ulrich Zeilhofer
(3)
,
Ulrike Müller
(1)
1
Max Planck Institute for Brain Research
2 UCL - University College London [UCL]
3 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
4 UKB - Universitätsklinikum Bonn
5 NCI - Neurophysiologie cellulaire et intégrée
6 UZH - Universität Zürich [Zürich] = University of Zurich
2 UCL - University College London [UCL]
3 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
4 UKB - Universitätsklinikum Bonn
5 NCI - Neurophysiologie cellulaire et intégrée
6 UZH - Universität Zürich [Zürich] = University of Zurich
Pierrick Poisbeau
- Fonction : Auteur
- PersonId : 1517556
- IdHAL : poisbeau
- ORCID : 0000-0002-6089-9201
- IdRef : 069369674
Hanns Ulrich Zeilhofer
- Fonction : Auteur
- PersonId : 1278258
- ORCID : 0000-0001-6954-4629
Résumé
Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR alpha3 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 alpha3 may provide a previously unrecognized molecular target in pain therapy.