Background and aims: Patients with inflammatory bowel disease often present with abnormal gut motility away from the inflammatory site. We studied remote motility disturbances and their pathophysiology in a rat model of colitis.
Methods: Colitis was induced 72 h prior to experiments using trinitrobenzene sulphate (TNBS) instillation. Inflammation was verified using histology and myeloperoxidase (MPO) measurements. To assess gut motility, we determined gastric emptying, distal front and geometric centre (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. The effects of hexamethonium (20 mg/kg), capsaicin (125 mg/kg) and pelvic nerve section on colitis induced motility changes were evaluated. c-Fos expression was studied in the pelvic nerve dorsal root ganglion (DRG) S1.
Results: Colitis reduced gastric emptying from 38.4 (3.6)% in controls to 22.7 (4.4)% in TNBS treated rats in the absence of local gastric inflammation. Colitis had no effect on the distal front or on the geometric centre of small intestinal transit. Hexamethonium reduced gastric emptying in controls to 26.3 (4.1)% but restored it to 35.8 (4.4)% in TNBS treated rats. Capsaicin significantly impaired gastric emptying in controls from 33.1 (5.2)% to 9.5 (3.3)% while this effect was less pronounced in TNBS treated rats (from 19.2 (2.3)% to 11.5 (3.8)%; NS). In TNBS treated rats, pelvic nerve section completely restored gastric emptying from 19.8 (5.3)% to 52.5 (6.3)% without any effect on gastric emptying in control rats. TNBS colitis induced de novo c-Fos expression in the DRG S1.
Conclusions: Experimental colitis in rats delays gastric emptying via a neuronal pathway involving pelvic afferent nerve hyperactivity.
- ANOVA, analysis of variance
- CGRP, calcitonin gene related peptide
- DRG, dorsal root ganglion
- GCS+I, geometric centre of stomach and intestine
- GCI, geometric centre of intestine
- IBD, inflammatory bowel disease
- MPO, myeloperoxidase
- PBS, phosphate buffered saline
- TNBS, trinitrobenzene sulphate
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Published Online First 14 September 2006
Funding: Heiko De Schepper is an aspirant of the Fund for Scientific Research, Flanders (FWO). This work was supported financially by the interuniversity Poles of Attraction (IUPA) program P5/20 and by the FWO (grant No G.0200.05).
Conflict of interest: None.
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