Biochemical and Biophysical Research Communications
The impact of CREB and its phosphorylation at Ser142 on inflammatory nociception
Section snippets
Materials and methods
Animals. Experimentally naive male Sprague–Dawley rats (Charles River, Sulzfeld, Germany) weighing 150–200 g at the time of surgery were used for antisense knock down of CREB. Mice with a mutation in the CREB serine 142 phosphorylation site where serine is exchanged for alanine (CREB S142A mice) and wild-type control mice were kindly provided by Prof. Günther Schütz, DKFZ Heidelberg. These mice are viable and fertile and show no obvious abnormalities in size or morphology in comparison to
Nociceptive behaviour after CREB antisense knock down in the rat spinal cord
The role of CREB in nociceptive transmission has been evaluated by investigation of the CFA-induced thermal hyperalgesia in rats treated either with CREB-sense or -antisense-oligonucleotides. Spinal perfusion with the CREB-antisense-oligonucleotide caused a significant reduction of CREB protein in the lumbar spinal cord as compared to treatment with sense-oligonucleotides (Fig. 1A). At baseline the two groups showed no differences in the paw withdrawal latency (PWL) in response to a thermal
Discussion
Several studies have shown that the activation of CREB in spinal cord dorsal horn neurons plays a central role in the transmission of nociceptive stimuli and long term adaptive responses in the central nervous system [3], [5], [22]. CREB is a constitutive transcription factor which is activated by phosphorylation through various kinases including PKA, PKC, Erk, p38 MAPK, and PKG that all contribute to the immediate adaptation to nociceptive input. Supporting this view we show here, that
Acknowledgments
The authors thank Christine Manderscheid for excellent technical assistance as well as Prof. Günther Schütz, DKFZ Heidelberg, Germany, for kindly providing CREB S142A mice and antibody against phospho-CREB (Serine 142). The study was supported by the Deutsche Forschungsgemeinschaft DFG (GE 695/2-2).
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