Activation of the ERK1/2 signaling cascade by excitotoxic spinal cord injury

Chen Guang Yu, Robert P. Yezierski

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


The role of the ERK1/2 signal transduction pathway and related transcription factors in the regulation of gene expression and pain behavior following excitotoxic spinal cord injury (SCI) was examined. Specifically, phosphorylation of ERK1/2, activation of transcription factors NF-kB, ELK-1, and CREB, and gene expression of the neurokinin-1 receptor and NMDA receptor subunits NR1 and NR-2A were investigated. Excitotoxic injury was produced by intraspinal injection of quisqualic acid (QUIS) in male Sprague-Dawley rats. Western blots were used to evaluate phosphorylation and activation of ERK1/2 and transcription factors using phospho-specific or total antibodies. Real-time PCR was used to evaluate gene expression of NK-1R, NR-1, and NR-2A. Assessment of excessive grooming behavior was used to evaluate the presence of spontaneous pain behavior. Excitotoxic spinal injury resulted in: (1) increased phosphorylation of ERK1/2; (2) increased activation of NF-kB and phosphorylation of ELK-1; and (3) increased gene expression for the NK-1 receptor and NR1 and NR-2A subunits of the NMDA receptor. Blockade of the ERK cascade with the MEK inhibitor PD98059 inhibited phosphorylation of ELK-1, activation of NF-kB and gene expression of NR1, NR-2A and NK-1R, and prevented the development of excessive grooming behavior. The results have shown that excitotoxic spinal injury leads to the injury-induced activation of the ERK→ELK-1 and NF-kB signaling cascades and transcriptional regulation of receptors important in the development of chronic pain. Blockade of this intracellular kinase cascade prevented the onset of injury-induced pain behavior.

Original languageEnglish
Pages (from-to)244-255
Number of pages12
JournalMolecular Brain Research
Issue number2
StatePublished - Aug 18 2005

Bibliographical note

Funding Information:
This work was supported by NS40096 and the University of Florida and McKnight Brain Institute Neurotrauma Research Program.


  • ERK
  • Excitotoxicity
  • Gene expression
  • Glutamate receptor
  • Pain
  • Spinal cord injury

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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