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Endogenous ephrinB2 mediates colon-urethra cross-organ sensitization via Src kinase-dependent tyrosine

Hsien-Yu Peng1, Gin-Den Chen, Cheng-Hung Lai

  • 1Department of Physiology, College of Medicine, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan.

American Journal of Physiology. Renal Physiology
|October 30, 2009
PubMed

Insights

EphB receptor (EphBR) and ephrinB interactions in the spinal cord drive pain sensitization between the colon and urethra. This involves Src-family kinase-dependent NMDAR NR2B phosphorylation, contributing to referred pain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pain Research

Background:

  • EphB receptor tyrosine kinase and ephrinB ligands are implicated in spinal pain-related neural plasticity.
  • The mechanisms linking colon-urethra cross-organ sensitization to spinal cord pathways remain unclear.

Purpose of the Study:

  • To investigate if Src-family kinase-dependent N-methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation mediates lumbosacral spinal EphB receptor (EphBR) activation.
  • To determine the role of EphBR activation in cross-organ sensitization between the colon and urethra.

Main Methods:

  • External urethral sphincter electromyogram activity was recorded following pelvic nerve stimulation.
  • Protein expression and phosphorylation in the lumbosacral (L6-S2) dorsal horn were analyzed before and after intracolonic mustard oil (MO) instillation.
  • The effects of intrathecal EphB1/B2 fusion protein and PP2 on reflex sensitization and NR2B phosphorylation were evaluated.

Main Results:

  • Intracolonic MO instillation induced colon-urethra reflex sensitization.
  • MO instillation upregulated endogenous ephrinB2 expression and increased phosphorylation of EphB 1/2, Src-family kinase, and NR2B tyrosine residues.
  • Intrathecal EphB1/B2 fusion protein and PP2 treatment reversed MO-induced reflex sensitization and NR2B phosphorylation.

Conclusions:

  • EphB receptor-ephrinB interactions in the lumbosacral spinal cord contribute to colon-urethra cross-organ sensitization.
  • Src-family kinase-dependent NMDAR NR2B phosphorylation is a key mechanism in this process.
  • These findings elucidate pathways involved in viscero-visceral referred pain between the bowel and urethra.

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