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

Jing Wu23, Guangxiao Su1, Long Ma1, Xuan Zhang3, Yongzhong Lei1, Junfa Li4, Qing Lin3 and Li Fang13*

Author Affiliations

1 Division of Neurosurgery, Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0517; USA

2 Department of Neurology, University of Texas Health Science Center, Houston, TX77030-1501, USA

3 Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1043, USA

4 Institute for Biomedical Science of Pain, Department of Neurobiology, Capital University of Medical Sciences, Beijing 100054, China

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Molecular Pain 2005, 1:26  doi:10.1186/1744-8069-1-26

Published: 13 September 2005



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.


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.


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.

Central sensitization; transcription factors; protein kinase cascade; nociception