Z Gastroenterol 2009; 47 - P167
DOI: 10.1055/s-0029-1241417

Submucous rather than myenteric neurons are activated by supernatants of mucosal biopsies from IBS patients

Q Li 1, S Buhner 1, S Vignali 1, G Barbara 2, R De Giorgio 2, V Stanghellini 2, K Michel 1, M Schemann 1
  • 1Technische Universität München, Humanbiologie, Freising Weihenstephan, Germany
  • 2St. Orsola Hospital, Bologna, Department of Internal Medicine and Gastroenterology, Bologna, Italy

Introduction: From our previous study we know that incubation supernatants of colonic mucosal biopsies from patients with Irritable Bowel Syndrome (IBS) activate neurons of the human submucous plexus.

Objectives: We used an animal model in guinea pigs to clarify whether the nerve sensitizing effect of IBS supernatants is also obvious in myenteric neurons. We therefore studied the effects of supernatants released from mucosal biopsies of 6 IBS patients (3 C-IBS and 3 D-IBS) and 4 healthy control persons (HC).

Methods: A fast neuroimaging technique with a voltage sensitive dye (Di-8-ANEPPS) was used to record single cell activity of submucous and myenteric neurons of the guinea pig after local spritz-application of C- and D- IBS supernatants as well as HC supernatants. Neuronal activity was studied in preparations from 96 guinea pigs and 3328 neurons.

Results: Neither in submucous nor in myenteric neurons control supernatants evoked a significant response. Five out of 280 submucous neurons showed an action potential discharge after HC application yielding spike frequency of 0.08Hz. Myenteric neurons did not respond at all to HC (n=54 neurons). In contrast supernatants from all IBS patients significantly increased spike discharge in guinea pig submucous and myenteric neurons. However, myenteric neurons responded significantly weaker compared to the submucous neurons. The percentage of responding neurons was less than half (4%; (interquartile range 0–16%) n=1171 neurons vs. 48%; (31–63%); n=2157 neurons) and the spike frequency was significantly lower for each of the IBS supernatants (1.7Hz; (1.3–2.6Hz) vs. 3.6Hz, (2.4–5.3Hz); Mann-Whitney Rank Sum Test). There was no difference between C and D IBS effects. Both, the submucous and the myenteric neuronal responses seem to be predominantly mediated by proteases.

Conclusion: Our results show that supernatants from IBS but not from control biopsies contain soluble mediators that evoke excitation in guinea pig submucous and myenteric neurons. However, this excitation seems to be primarily a feature of submucous rather than myenteric neurons.