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Published in: Molecular Pain 1/2005

Open Access 01-12-2005 | Research

Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection

Authors: Jing Wu, Guangxiao Su, Long Ma, Xuan Zhang, Yongzhong Lei, Junfa Li, Qing Lin, Li Fang

Published in: Molecular Pain | Issue 1/2005

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Abstract

Background

Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection.

Results

We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group.

Conclusion

These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.
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Metadata
Title
Protein kinases mediate increment of the phosphorylation of cyclic AMP -responsive element binding protein in spinal cord of rats following capsaicin injection
Authors
Jing Wu
Guangxiao Su
Long Ma
Xuan Zhang
Yongzhong Lei
Junfa Li
Qing Lin
Li Fang
Publication date
01-12-2005
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2005
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-1-26

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