Abstract no.: 4 Experimental inflammation of the colon modulates stomach motility via neuronal pathways

Abstract

Patients with IBD often suffer from impaired gastrointestinal motility, even at sites remote from the inflammation. We previously reported diminished gastric emptying associated with reduced gastric fundus contractility in rats with TNBS‐induced colitis. The aims of the present study were (1) to exclude local gastric inflammation using MPO measurements and to rule out direct systemic influences on gastric neuromuscular function by examining the effect of TNBS‐induced colitis on contractions of aortic vascular rings. Secondly (2) we tested the involvement of neuronal ganglionic (nicotinic) transmission and of extrinsic reflex pathways in impaired gastric emptying in rats with TNBS‐induced colitis. Distal colitis was induced by rectal instillation of 30 mg trinitrobenzene sulphate (TNBS) in 50% ethanol 72 h prior to experiments. Gastric emptying (GE) and the geometric center (GC) of intestinal transit were measured 30 min after intragastric injection of a semiliquid bolus of Evans blue. TNBS colitis reduced gastric emptying from 38.4 ± 3.6% in controls to 22.7 ± 4.4% but had no effect on small intestinal transit. (1) Myeloperoxidase (MPO) measurements revealed no acute inflammatory changes in the stomach whereas MPO was significantly increased in the colon of TNBS rats. The study of aortic ring contractility showed no differences between control rats and rats with TNBS colitis. (2) The nicotinic receptor blocker hexamethonium (20 mg/kg ip 1 h prior to experiment) inhibited GE by 31% in controls (P < 0.05) whereas it increased GE by 37% in TNBS rats (P < 0.05). The GC of gastrointestinal transit was similarly affected. Extrinsic afferent innervation was abolished by capsaicin pre‐treatment (50 mg/kg SC 14 days prior to experiment). Capsaicin reduced GE by 71% in control rats (P < 0.05) while in TNBS rats its effect on GE was no longer significant (40% reduction). Capsaicin pre‐treatment had comparable effects on the GC of gastrointestinal transit in controls and TNBS. In conclusion, we showed that TNBS colitis induces a pronounced gastroparesis which is not due to local gastric inflammation nor to systemic impairment of neuromuscular function. Moreover, it involves nicotinic synapses embedded in autonomic reflexes. A role for extrinsic afferent pathways sensitized by inflammatory mediators seems plausible.