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Phosphorylation of extracellular signal-regulated kinases in bladder afferent pathways with cyclophosphamide-induced

K A Corrow1, M A Vizzard

  • 1Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA.

Neuroscience
|July 30, 2009
PubMed

Insights

Extracellular signal-regulated kinases (ERK1/2) are activated in the nervous system during inflammation. This study shows ERK1/2 activation in specific dorsal root ganglia (DRG) contributes to cystitis-induced pain signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Urology

Background:

  • Extracellular signal-regulated kinases (ERK1 and ERK2) are crucial signaling molecules in the nervous system, involved in processes like central sensitization and pain hypersensitivity.
  • ERK1/2 activation has been observed in the urinary bladder following cyclophosphamide (CYP)-induced cystitis, and its inhibition can reduce associated bladder hyperreflexia.

Purpose of the Study:

  • To investigate the expression and regulation of phosphorylated extracellular signal-regulated kinases (pERK1/2) in the lumbosacral dorsal root ganglia (DRG) and spinal cord.
  • To determine the role of pERK1/2 in CYP-induced cystitis at different time points (4 h, 48 h, chronic).

Main Methods:

  • Western blotting and immunohistochemical techniques were employed to analyze pERK1/2 expression.
  • Experiments were conducted on rats with CYP-induced cystitis at 4 hours, 48 hours, and chronic time points.

Main Results:

  • pERK1/2 expression was significantly upregulated in L6 and S1 DRG at 4 hours post-CYP administration, with no changes observed in other DRG or spinal cord segments.
  • Cytoplasmic pERK1/2-immunoreactivity (IR) increased significantly in L6 and S1 DRG at 4 and 48 hours, while pericellular pERK1/2-IR remained unchanged.
  • CYP-induced cystitis significantly increased the percentage of bladder afferent cells in L6 and S1 DRG expressing pERK1/2-IR at 48 hours.

Conclusions:

  • Activation of the ERK pathway in the lumbosacral DRG, particularly in L6 and S1 DRG, appears to play a significant role in the neuroplasticity of micturition reflexes during CYP-induced cystitis.
  • These findings highlight the involvement of specific DRG segments in the pain signaling associated with bladder inflammation.

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