title: Downregulation of cytosolic prostaglandin E2 synthase results in decreased nociceptive behavior in rats.
abstract: Nociception-evoked prostaglandin E2 (PGE2) release in the spinal cord contributes considerably to the development of hyperalgesia and allodynia. Biosynthesis of PGE2 involves the conversion of arachidonic acid to PGH2 by cyclooxygenases (COXs), followed by an isomerization of PGH2 to PGE2 by PGE2 synthases (PGESs). The roles of COX-1, COX-2, and the inducible microsomal PGES-1 have been studied in models of pain and inflammation. In contrast, in nociceptive processes, very little is known about the role of cytosolic PGES (cPGES), which has been described as being functionally coupled to COX-1. Here we show by in situ hybridization and immunohistological analysis that COX-1 and cPGES are constitutively expressed in neuronal and non-neuronal cells of the dorsal and ventral horns in the spinal cord of adult rats. The protein levels of both enzymes were not regulated by nociceptive stimuli; however, reduction of cPGES in rat spinal cord with intrathecal application of cPGES antisense oligonucleotides reduced the nociceptive behavior in zymosan-evoked thermal hyperalgesia and in the formalin assay. The data indicate that cPGES plays an important role in mediating early responses during spinal nociceptive processing.
authors.affiliation: Pharmazentrum Frankfurt, Zentrum für Arzneimittelforschung, Entwicklung, und Sicherheit, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, 60590 Frankfurt, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Hofacker
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Coste
authors.forename: Hong-Van
authors.initials: HV
authors.lastname: Nguyen
authors.forename: Claudiu
authors.initials: C
authors.lastname: Marian
authors.forename: Klaus
authors.initials: K
authors.lastname: Scholich
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1 / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D015536:Down-Regulation; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D000071876:Prostaglandin-E Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D015054:Zymosan
chemical_list: D016376:Oligonucleotides, Antisense; D015054:Zymosan; D051545:Cyclooxygenase 1; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases