Jan Brun

Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients

Background  Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi‐factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract.

Exploration of the effects of gender and mild esophagitis on esophageal pain thresholds in the normal and sensitized state of asymptomatic young volunteers

Clinical data suggest gender differences in gastrointestinal pain, but very little experimental data exist. Esophageal painful thresholds to mechanical, thermal, electric, and chemical stimuli can be measured with the esophageal multimodal pain model. The aim was to measure the effect of gender and mild esophagitis on esophageal pain perception.

Modality specific alterations of esophageal sensitivity caused by longstanding diabetes mellitus

Abstract Background Abnormal visceral sensory function has been demonstrated in patients with diabetes mellitus and diabetic autonomic neuropathy seems to be involved in the development and progression of gastrointestinal tract dysfunction. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in, e.g. the esophagus has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favours investigation of central pain mechanisms involved in allodynia and hyperalgesia. Hence the rationale of the presents study was to explore the nervous system by assessment of esophageal sensitivity to multimodal stimulations. Methods Throughout an euglycemic clamp, 31 healthy volunteers (age 44.3 ± 10.6 (mean ± SD) years; 11men) and 31 patients (age 46.3 ± 11.7 years; 10 men) with insulin dependent diabetes mellitus (duration 31.3 ± 13.1 years) were included in the study. By use of a multimodal oesophageal probe, sensitivity to heat, mechanical distension and electrical stimulation was assessed in the lower oesophagus. Results For heat stimulation patients had increased sensitivity in the sensory range with shorter stimulus duration until pain tolerance threshold (122 ± 3.8 sec vs. 136 ± 3.7 sec; p = 0.006) and larger area under the temperature curve (2380 ± 1847 vs. 1409 ± 1450; p = 0.03). There were no differences between groups for mechanical stimulation (maximum pressure (39 ± 57mmHg vs. 24 ± 48mmHg; p = 0.3; maximum volume 59 ± 21ml vs. 62 ± 25 ml; p = 0.56). As an overall finding, patients tolerated higher electrical stimulation intensities (p = 0.02), dominated by discrimination in the sensory range: At sensory detection threshold (VAS1) 21.1 ± 12.4 mA vs. 16.3 ± 5.5 mA (p = 0.03); at moderate sensation (VAS3) 27.5 ± 13.3 mA vs. 21.5 ± 5.0 mA (p = 0.03) however at pain detection threshold (VAS5) 31.6 ± 13.1mA vs. 28.8 ± 5.2 mA; the trend was insignificant (p = 0.3). Conclusion Patients with insulin dependent diabetes mellitus had modality-specific alterations of esophageal sensitivity. Heat stimulation activates selectively mucosal receptors whereas on the contrary electrical stimulation depolarizes the free nerve endings non-selectively. Hence, due to the different sensitivity profile, the esophageal neuropathy is most likely a result of both peripheral and central neuropathy caused by longstanding diabetic neuronal damage.