Publication Date:
2004-05-08
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harvey, Robert J -- Depner, Ulrike B -- Wassle, Heinz -- Ahmadi, Seifollah -- Heindl, Cornelia -- Reinold, Heiko -- Smart, Trevor G -- Harvey, Kirsten -- Schutz, Burkhard -- Abo-Salem, Osama M -- Zimmer, Andreas -- Poisbeau, Pierrick -- Welzl, Hans -- Wolfer, David P -- Betz, Heinrich -- Zeilhofer, Hanns Ulrich -- Muller, Ulrike -- New York, N.Y. -- Science. 2004 May 7;304(5672):884-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15131310" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Cell Line
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Dinoprostone/administration & dosage/*metabolism/pharmacology
;
Female
;
Freund's Adjuvant
;
Glycine/metabolism
;
Humans
;
Inflammation/metabolism/*physiopathology
;
Male
;
Mice
;
Mice, Knockout
;
Molecular Sequence Data
;
Neurons/metabolism
;
Pain/*physiopathology
;
Patch-Clamp Techniques
;
Phosphorylation
;
Posterior Horn Cells/*metabolism
;
Receptors, Glycine/chemistry/genetics/*metabolism
;
Signal Transduction
;
Spinal Cord/*metabolism
;
Synaptic Transmission
;
Transfection
;
Zymosan
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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