Up-regulation of calcitonin gene-related peptide and receptor tyrosine kinase TrkB in rat bladder afferent neurons following TNBS colitis

Exp Neurol. 2007 Apr;204(2):667-79. doi: 10.1016/j.expneurol.2006.12.024. Epub 2007 Jan 11.

Abstract

Colonic inflammation has profound effects on the urinary bladder physiology and produces hypersensitivity of bladder afferent neurons and neurogenic bladder overactivity. Calcitonin gene-related peptide (CGRP) expressed in dorsal root ganglia (DRG) plays an important role in mediating sensory perception following visceral inflammation. In the present study, we determined that the expression of CGRP was increased in bladder afferent neurons in lumbosacral DRG following tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in rat. After colitis, the percentage of bladder afferent neurons expressing CGRP was increased in L1 (61.2+/-2.9% in colitis vs. 37.7+/-5.1% in controls; p<0.05) and S1 DRG (26.3+/-2.3% in colitis vs. 15.5+/-1.9% in controls; p<0.01). We also demonstrated that the expression of tyrosine kinase receptor TrkB was increased in L1 (39.7+/-2.9% in colitis vs. 25.2+/-4.3% in controls; p<0.05) and S1 DRG (45.6+/-3.8% in colitis vs. 38.3+/-3.6% in controls; p<0.01) following colitis. CGRP and TrkB were co-stored in a subpopulation of DRG neurons in control and colitic animals and the number of DRG cells co-expressing CGRP and TrkB was significantly increased in L1 (2.7-fold, p<0.01) and S1 DRG (2.4-fold, p<0.01) following colitis. In cultured DRG, exogenous BDNF application significantly increased CGRP expression, which was blocked by TrkB selective inhibitor K252a. These results suggest that up-regulation of CGRP and TrkB in bladder afferent neurons may play a role in colon-to-bladder cross-sensitization following colitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / metabolism
  • Analysis of Variance
  • Animals
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / metabolism*
  • Carbocyanines / metabolism
  • Cells, Cultured
  • Colitis* / chemically induced
  • Colitis* / pathology
  • Colitis* / physiopathology
  • Ganglia, Spinal / cytology
  • Gene Expression Regulation / drug effects
  • Male
  • Methacrylates*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism*
  • Up-Regulation / drug effects*
  • Urinary Bladder / innervation*

Substances

  • 3,3'-dihexadecylindocarbocyanine
  • Amidines
  • Carbocyanines
  • Methacrylates
  • diamidino compound 253-50
  • tri-n-butylstannylmethacrylate
  • Receptor, trkB
  • Calcitonin Gene-Related Peptide