title: The impact of CREB and its phosphorylation at Ser142 on inflammatory nociception.
abstract: Peripheral noxious stimulation leads to phosphorylation and thereby activation of the transcription factor CREB in the spinal cord. CREB phosphorylation occurs mainly at serine 133, but the phosphorylation site at serine 142 may also be important. We investigated the impact of spinal CREB protein levels and phosphorylation at Ser142 on the nociceptive behaviour in rat and mouse models of inflammatory nociception. Downregulation of total CREB protein in the rat spinal cord by antisense-oligonucleotides resulted in antinociceptive effects. After peripheral noxious stimulation CREB was phosphorylated in the spinal cord at serine 133 and 142 indicating a potential role of both residues in nociceptive processing. However, Ser142 mutant mice developed equal behavioural correlates of hyperalgesia as wild-type mice in different inflammatory models. Thus, our data confirm that CREB is essential for spinal nociceptive processing. However, prevention of phosphorylation only at serine 142 is not sufficient to modulate the nociceptive response.
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: e.niederberger@em.uni-frankfurt.de.
authors: Ellen
authors: E
authors: Niederberger
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Corina
authors: C
authors: Ehnert
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Wei
authors: W
authors: Gao
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Ovidiu
authors: O
authors: Coste
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Achim
authors: A
authors: Schmidtko
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Laura
authors: L
authors: Popp
authors: Dr. Senckenbergische Anatomie, Fachbereich Medizin, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors: Charlotte von
authors: CV
authors: Gall
authors: Dr. Senckenbergische Anatomie, Fachbereich Medizin, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
authors: Horst Werner
authors: HW
authors: Korf
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Irmgard
authors: I
authors: Tegeder
authors: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
authors: Gerd
authors: G
authors: Geisslinger
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000502:physiology; D015536:Down-Regulation; D007249:Inflammation; D008297:Male; D051379:Mice; D009154:Mutation; D010146:Pain; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000737:chemistry*; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016760:Proto-Oncogene Proteins c-fos; D012694:Serine