GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization.
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.
Harvey
Robert J
RJ
Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.
Depner
Ulrike B
UB
Wässle
Heinz
H
Ahmadi
Seifollah
S
Heindl
Cornelia
C
Reinold
Heiko
H
Smart
Trevor G
TG
Harvey
Kirsten
K
Schütz
Burkhard
B
Abo-Salem
Osama M
OM
Zimmer
Andreas
A
Poisbeau
Pierrick
P
Welzl
Hans
H
Wolfer
David P
DP
Betz
Heinrich
H
Zeilhofer
Hanns Ulrich
HU
Müller
Ulrike
U
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
D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit; D005620:Freund's Adjuvant; D015054:Zymosan; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D005998:Glycine