Lay Summary

Proposal No.  IBD-0086R2
Principal Investigator:  Robin Spiller, M.D.
Applicant Organization:  University of Nottingham (United Kingdom)
Project Title:  Altered enteric nerve phenotype and visceral sensation in inflammatory bowel disease
Period of Award:  August 1, 2005 – January 1, 2007

Chronic recurrent abdominal pain and alteration in bowel habit are debilitating symptoms frequently seen in patients with inflammatory bowel disease (IBD) that can continue even when the inflammation has resolved.  The mechanisms underlying these symptoms are unknown and, as a result, current therapeutic options such as dietary manipulation, antispasmodics and possibly surgery are largely ineffective.  However, as these symptoms occur in the absence of inflammation, it is possible that they are the result of an increased sensitivity of the intestine.

We have previously demonstrated that patients with diverticular disease experience similar symptoms and our work suggests that these may be the result of previous inflammatory damage to the nerves in the lining of the colon.

Our study aims to explore the relationship between these nerve changes and their correlation to:

  • the symptoms experienced by patients with quiescent ulcerative colitis
  • the sensitivity of the rectum in these patients


We plan to do this by asking patients with quiescent ulcerative colitis about their current bowel habits and symptoms, followed by a telescopic examination of the rectum to obtain samples of the lining of the bowel.  This will allow us to visualize the nerves and to demonstrate the level of neuropeptides and receptors expressed by them.  Using well described methods, we will test the sensitivity of the rectum in selected patients to two stimuli (stretch and chemical stimulation).

We predict that symptomatic patients will have increased neuropeptide staining and decreased levels of stimulation required to elicit an initial sensation of pain compared with the asymptomatic groups and healthy controls.

This research would be regarded as a major step in the development of effective therapeutic strategies in IBD, as it allows the problem of persisting symptoms during remission of inflammation to be approached from an original angle.  Similar research in patients with hypersensitive bladders has resulted in the successful therapeutic use of novel analgesic agents, including resiniferatoxin.