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Background According to the Chicago classification of esophageal motility disorders, distal esophageal spasm ( DES) is defined as premature esophageal contractions (distal latency [ DL] <4.5 s) for ≥20% of swallows, in the presence of a normal mean integral relaxation pressure ( IRP). However, some patients with symptoms of DES have rapid contractions with a normal DL. The aim of this study was to characterize these patients and compare their clinical characteristics to those of patients classified as DES. Methods We retrospectively compared clinical characteristics and high-resolution manometry findings of patients with rapid contractions with normal latency to those meeting the Chicago classification criteria for DES. Key Results Over a 3-year period, nine patients were diagnosed with DES and 14 showed rapid contractions in the distal esophagus with normal latency. The latter were younger than DES patients (60 ± 4 vs 72 ± 3 years, p < 0.05). Dysphagia and retrosternal pain occurred to a similar degree in both groups. Weight loss and abnormal barium esophagogram tended to be more frequent in DES patients. There was no difference in contractile front velocity ( CFV) and in distal contractile integral ( DCI) between patients with DES and rapid contractions with normal latency. Lower esophageal sphincter pressures were not different between groups. However, IRP was significantly higher in DES compared to rapid contractions with normal latency (11.7 ± 0.6 mmHg vs 7.6 ± 1.2 mmHg, p < 0.05), albeit still within the normal range. Conclusions & Inferences These data suggest that patients with simultaneous contractions with normal latency represent a group of patients with many features similar to DES. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation. Colitis was induced by trinitrobenzene sulfate (TNBS) instillation. We determined GE, distal front, and geometric center (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. We evaluated the effects of the transient receptor potential vanilloid type 1 (TRPV1) antagonists capsazepine (5-10 mg/kg) and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)carboxamide (BCTC; 1-10 mg/kg) and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (150 microg/kg). To determine TRPV1 receptor antagonist sensitivity, we examined their effect on capsaicin-induced relaxations of isolated gastric fundus muscle strips. Immunocytochemical staining of TRPV1 and RT-PCR analysis of TRPV1 mRNA were performed in dorsal root ganglion (DRG) L6-S1. TNBS-induced colitis reduced GE but had no effect on intestinal motility. Capsazepine reduced GE in controls but had no effect in rats with colitis. At doses that had no effects in controls, BCTC and CGRP-(8-37) significantly improved colitis-induced gastroparesis. Capsazepine inhibited capsaicin-induced relaxations by 35% whereas BCTC completely abolished them. TNBS-induced colitis increased TRPV1-like immunoreactivity and TRPV1 mRNA content in pelvic afferent neuronal cell bodies in DRG L6-S1. In conclusion, distal colitis in rats impairs GE via sensitized pelvic afferent neurons. We provided pharmacological, immunocytochemical, and molecular biological evidence that this sensitization is mediated by TRPV1 receptors and involves CGRP release.