Submitted on August 5, 2008
Revised on February 10, 2009
Accepted on February 10, 2009
Alterations to enteric neural signaling underlie secretory abnormalities of the ileum in experimental colitis in the guinea pig
Ian M Hons1, Joshua E Burda1, John R Grider2, Gary M. Mawe3, and Keith A Sharkey1*
1 University of Calgary
2 Virginia Commonwealth University
3 University of Vermont
* To whom correspondence should be addressed. E-mail: ksharkey{at}ucalgary.ca.
Inflammatory bowel diseases (IBD) can involve widespread gastrointestinal dysfunction, even in cases where inflammation is localized to a single site. The underlying pathophysiology of dysfunction in non-inflamed regions is unclear. We examined whether colitis is associated with altered electrogenic ion transport in the ileal mucosa and/or changes in the properties of ileal submucosal neurons. Colitis was induced by administration of trinitrobenzene sulphonic acid (TNBS) and the uninflamed ileum from animals was examined 3, 7 and 28 days later. Electrogenic ion transport was assessed in Ussing chambers. Intracellular microelectrode recordings were used to examine the neurophysiology of the submucosal plexus of the ileum in animals with colitis. Non-cholinergic secretion was reduced by 33% in the ileum from animals 7 days after the induction of colitis. The epithelial response to vasoactive intestinal peptide (VIP) was unaltered in animals with colitis, but the response to carbachol was enhanced. Slow excitatory synaptic transmission was dramatically reduced in VIP-expressing, non-cholinergic secretomotor neurons. This change was detected as early as 3 days following TNBS treatment. No changes to fast synaptic transmission or the number of VIP neurons were observed. In addition, cholinergic secretomotor neurons fired more action potentials during a given stimulus and intrinsic primary afferent neurons had broader action potentials in animals with colitis. These findings implicate changes to enteric neural circuits as contributing factors in inflammation-induced secretory dysfunction at sites proximal to a localized inflammatory insult.
