The optimal order of stimulation modalities and reproducibility of the multimodal esophageal stimulation paradigm

Abstract

Background Esophageal hypersensitivity can be triggered by different stimuli. We use a multimodal stimulation model to study esophageal sensitivity to four sensory modalities: thermal, mechanical, electrical, and chemical stimulation. The optimal order of these stimulations needs further validation. Methods Esophageal sensitivity to thermal (heated saline solution), mechanical (balloon distention), electrical (block pulses with electrodes), and chemical stimulation (acid solution, 0.1 N HCl) was assessed in 10 subjects. In one session, thermal stimulation was performed first, followed by mechanical stimulation (“original protocol”). In a second session, mechanical stimulation was performed first, followed by temperature stimulation (“reversed protocol”). Besides, the impact of balloon distention speed (25 mL/min vs 50 mL/min) during mechanical stimulation was evaluated. Secondly, in order to establish reproducibility, independent control sessions of multimodal stimulations in 15 healthy volunteers were used retrospectively. Key results A significant difference in pain perception threshold for thermal stimulation was found between the original and reversed protocol (P = 0.046), indicating that mechanical stimulation can sensitize the esophagus to thermal stimulation. Balloon distention rate had no impact on sensitivity thresholds for mechanical stimulation. Concerning the reproducibility, there were no differences for thermal, mechanical, electrical, and chemical stimulation in any of the control sessions. Conclusions The optimal order of the multimodal stimulation protocol was to start with the thermal stimulation, followed by mechanical, electrical, and chemical stimulation. The optimal balloon distention rate was 25 mL/min. Multimodal esophageal stimulation generates reproducible perception scores in health and therefore provides a reliable method to assess esophageal sensitivity changes after interventions that may alter esophageal sensitivity.

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health

“…Sample sizes were based on previously performed studies with the same technique in our group and the group from Denmark. [21][22][23]26,27 A p-value <0.05 was considered statistically significant. Data are presented as median [25th-75th percentiles], unless stated otherwise.…”

“…Next, esophageal sensitivity was evaluated by the multimodal esophageal stimulation probe (Ditens, Aalborg, Denmark), which allows stimulation of the esophagus in one single protocol and in the same order (thermal, mechanical, electrical, and chemical stimulation) as previously evaluated and reported. 22,23 During the four different esophageal stimulations, subjects were instructed to report perception of the stimuli using the visual analogue scale (VAS). Next, these numerical scores were interpreted as follows: VAS 1 = first perception threshold, VAS 5 = pain perception threshold (PPT), and VAS 7 = pain tolerance threshold (PTT).…”

“…Next, these numerical scores were interpreted as follows: VAS 1 = first perception threshold, VAS 5 = pain perception threshold (PPT), and VAS 7 = pain tolerance threshold (PTT). 21,23 Thermal stimulation was performed by recirculating a saline solution (0.9% NaCl) through the balloon mounted on the probe, and infusion water was heated by a water bath with a maximal temperature of 62°C. The volume in the balloon was kept constant at 5 ml to avoid mechanical stimulation of the esophagus.…”

“…After administration of the active product or placebo, a multimodal stimulation probe (as described in the technical note by Broers et al 21 ) was placed with the balloon positioned 10 cm proximal to the lower esophageal sphincter (LES). Next, esophageal sensitivity was evaluated by the multimodal esophageal stimulation probe (Ditens, Aalborg, Denmark), which allows stimulation of the esophagus in one single protocol and in the same order (thermal, mechanical, electrical, and chemical stimulation) as previously evaluated and reported 22,23 . During the four different esophageal stimulations, subjects were instructed to report perception of the stimuli using the visual analogue scale (VAS).…”

“…During the four different esophageal stimulations, subjects were instructed to report perception of the stimuli using the visual analogue scale (VAS). Next, these numerical scores were interpreted as follows: VAS 1 = first perception threshold, VAS 5 = pain perception threshold (PPT), and VAS 7 = pain tolerance threshold (PTT) 21,23 …”