title: GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization.
abstract: 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.
authors.affiliation: Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Depner
authors.forename: Heinz
authors.initials: H
authors.lastname: Wässle
authors.forename: Seifollah
authors.initials: S
authors.lastname: Ahmadi
authors.forename: Cornelia
authors.initials: C
authors.lastname: Heindl
authors.forename: Heiko
authors.initials: H
authors.lastname: Reinold
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Smart
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harvey
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schütz
authors.forename: Osama M
authors.initials: OM
authors.lastname: Abo-Salem
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Pierrick
authors.initials: P
authors.lastname: Poisbeau
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Betz
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005620:Freund's Adjuvant; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000378:metabolism*; D018009:Receptors, Glycine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism*; D009435:Synaptic Transmission; D014162:Transfection; D015054:Zymosan
chemical_list: D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit; D005620:Freund's Adjuvant; D015054:Zymosan; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D005998:Glycine