title: Colonic inflammation up-regulates voltage-gated sodium channels in bladder sensory neurons via activation of peripheral transient potential vanilloid 1 receptors.
abstract: BACKGROUND
  Primary sensory neurons express several types of ion channels including transient receptor potential vanilloid 1 (TRPV1) and voltage-gated Na(+) channels. Our previous studies showed an increased excitability of bladder primary sensory and spinal neurons triggered by inflammation in the distal colon as a result of pelvic organ cross-sensitization. The goal of this work was to determine the effects of TRPV1 receptor activation by potent agonists and/or colonic inflammation on voltage-gated Na(+) channels expressed in bladder sensory neurons.
  
  
  METHODS
  Sprague-Dawley rats were treated with intracolonic saline (control), resiniferatoxin (RTX, 10(-7 ) mol L(-1)), TNBS (colonic irritant) or double treatment (RTX followed by TNBS).
  
  
  RESULTS
  TNBS-induced colitis increased the amplitude of total Na(+) current by two-fold and of tetrodotoxin resistant (TTX-R) Na(+) current by 78% (P ≤ 0.05 to control) in lumbosacral bladder neurons during acute phase (3 days post-TNBS). Instillation of RTX in the distal colon caused an enhancement in the amplitude of total Na(+) current at -20 mV from -112.1 ± 18.7 pA/pF (control) to -183.6 ± 27.8 pA/pF (3 days post-RTX, P ≤ 0.05) without changes in TTX resistant component. The amplitude of net Na(+) current was also increased by 119% at day 3 in the group with double treatment (RTX followed by TNBS, P ≤ 0.05 to control) which was significantly higher than in either group with a single treatment.
  
  
  CONCLUSIONS
  These results provide evidence that colonic inflammation activates TRPV1 receptors at the peripheral sensory terminals leading to an up-regulation of voltage gated Na(+) channels on the cell soma of bladder sensory neurons. This mechanism may underlie the occurrence of peripheral cross-sensitization in the pelvis and functional chronic pelvic pain.
authors.affiliation: Division of Urology, Department of Surgery, University of Pennsylvania, Glenolden, PA 19036-2307, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Lei
authors.forename: A P
authors.initials: AP
authors.lastname: Malykhina
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004224:Diterpenes; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C024353:resiniferatoxin