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).

KEY 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 & INFERENCES:

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: Q Lei, A P Malykhina
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 24 Issue 6 Pg. 575-85, e257 (Jun 2012) ISSN: 1365-2982 [Electronic] England
• PMID: 22420642 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Diterpenes
• Sodium Channels
• TRPV Cation Channels
• TRPV1 receptor
• resiniferatoxin

Topics

• Animals
• Colitis (chemically induced, genetics, metabolism)
• Colon (drug effects, metabolism)
• Diterpenes (pharmacology)
• Male
• Rats
• Rats, Sprague-Dawley
• Sensory Receptor Cells (drug effects, metabolism)
• Sodium Channels (genetics, metabolism)
• TRPV Cation Channels (agonists, genetics, metabolism)
• Up-Regulation (drug effects, physiology)