Influence of naloxone on rectal sensorimotor function in health

Abstract  Abnormal rectal motor physiology and visceral hypersensitivity are implicated in the pathogenesis of irritable bowel syndrome. Endogenous opioids are involved in both the regulation of gut motility and the processing of sensory information. Our aim was to study the effect of suppression of endogenous opioid function by naloxone on rectal sensorimotor function in health. Eighteen healthy subjects participated in a rectal barostat study. Sensorimotor function was evaluated during two consecutive stepwise distensions separated by 30 min of basal tone recording, and with perception scoring on a 0–6 graded scale. Naloxone was administered, after 15 min of basal tone measurements, as an intravenous bolus (0.4 mg), followed by continuous infusion (20 μg kg⁻¹ h⁻¹) in a placebo-controlled, single-blinded and randomized fashion. Naloxone did not alter rectal sensitivity. Comparison of visual analogue scale scores between naloxone and saline did not reveal altered intensities of pain or discomfort. Compared to the baseline distension, a significant adaptive increase in compliance occurred during the second distension after saline (7.8 ± 0.7 vs 11.0 ± 0.6 mL mmHg⁻¹, P  = 0.0016). This dynamic change in rectal compliance did not occur after naloxone administration (8.8 ± 0.7 vs 10.1 ± 0.8 mL mmHg⁻¹, ns). Low intensity tonic distension induced a rectal adaptive relaxation, which was absent after naloxone. Naloxone does not alter rectal sensitivity but abolishes rectal adaptation in response to repeated balloon distention. These observations suggest that the endogenous opioid system is involved in control of rectal tone rather than rectal sensitivity.     

Oesophageal tone and sensation in the transition zone between proximal striated and distal smooth muscle oesophagus

Abstract  Previous studies have shown that the proximal striated muscle oesophagus is less compliant and more sensitive than the distal smooth muscle oesophagus. Conventional and high resolution manometry described a transition zone between striated and smooth muscle oesophagus. We aimed to evaluate oesophageal tone and sensitivity at the transition zone of oesophagus in healthy volunteers. In 18 subjects (seven men, mean age: 28 years) an oesophageal barostat study was performed. Tone and sensitivity were assessed using stepwise isobaric distensions with the balloon located at transition zone and at distal oesophagus in random order. To study the effect induced on transition zone by a previous distension at the distal oesophagus and vice versa, identical protocol was repeated after 7 days with inverted order. Initial distension of a region is referred to as 'naïf' distension and distension of a region following the distension of the other segment as 'primed' distension. Assessment of three oesophageal symptoms (chest pain, heartburn and 'other') was obtained at the end of every distension step. Compliance was significantly higher in the transition zone than in the distal oesophagus (1.47 ± 0.14 vs 1.09 ± 0.09 mL mmHg⁻¹, P  = 0.03) after 'naif' distensions. This difference was not observed during 'primed' distensions. Higher sensitivity at transition zone level was found in 11/18 (61%) subjects compared to 6/18 (33%, P  < 0.05) at smooth muscle oesophagus. Chest pain and 'other' symptom were more often induced by distention of the transition zone, whereas heartburn was equally triggered by distension of either region. The transition zone is more complaint and more sensitive than smooth muscle oesophagus.     

Symptom pattern and pathophysiological correlates of weight loss in tertiary-referred functional dyspepsia

Abstract  In patients with gastrointestinal symptoms, weight loss is an alarm symptom, indicative of organic disease. Recent studies reported weight loss in subsets of functional dyspepsia (FD) patients. The aim of this study was to analyse symptom patterns associated with weight loss in tertiary care FD. Six hundred and thirty-six FD patients (67% female, mean age 43 years) completed a dyspepsia questionnaire, and underwent gastric emptying and gastric barostat studies. After identifying independent symptom domains through orthogonal factor analysis, patients were clustered on the basis of symptom profile. Clusters were compared in terms of their association with weight loss and gastric emptying or sensorimotor function. Weight loss (4.2 kg on average) correlated most strongly with early satiety followed by nausea and vomiting ( ρ respectively 0.38, 0.28 and 0.23, all P  < 0.0001). Factor analysis revealed three factors: Factor 1 characterized by nausea, vomiting and early satiety; factor 2 by early satiety, postprandial fullness and bloating; and factor 3 by pain, epigastric burning and belching. Subsequent cluster analysis revealed six patient clusters. The most severe cluster, which loaded high on all three factors, and a cluster dominated factor 2 were associated with the highest average weight loss (6.8 and 8.0 kg, respectively). The former cluster was also characterized by visceral hypersensitivity and delayed gastric emptying. The lowest weight loss occurred in the two clusters that had depressed scores for both early satiety associated factors (2.4 and 2.5 kg, respectively). In tertiary care FD, weight loss is strongly associated with two early satiety associated symptom clusters.