International Society for Diseases of the Esophagus (ISDE) edition:14 location:Vancouver, Canada date:22-24 September 2014
ISDE VANCOUVER 2014 Abstract 669
"Esophageal sensitivity and visceral pain perception in health is not modulated by endogenous opioid release"
Background:When gastro-esophageal reflux is causing symptoms (heartburn, regurgitation) or lesions (esophagitis), it is defined as gastro-esophageal reflux disease (GERD). A large group of patients does not present with esophageal lesions and are referred to as non-erosive reflux disease patients (NERD). Proton pump inhibitors (PPI) are effective in healing esophagitis, but a large group of NERD patients remains symptomatic while taking PPIs. In these patients, esophageal hypersensitivity is considered an important pathophysiological mechanism and this is often linked to defective functioning of descending anti-nociceptive pathways, although evidence to support this hypothesis is lacking. Endogenous opioids are key candidate mediators of descending anti-nociception. Our aim was to study the role of centrally acting and peripherally restricted µ-opioid receptor antagonists naloxone and methylnaltrexone respectively on esophageal sensitivity in healthy volunteers (HV).
Methods:Esophageal multimodal sensitivity was quantified after administration of naloxone (20µg/kg/h IV infusion after 0.4mg bolus), methylnaltrexone (12mg/0.6ml SC injection) and placebo (0.9% NaCl) in 12 HV (7m/5f, mean age 31 y [range 22-51]). After an overnight fast, a custom made probe with a balloon was positioned in the distal esophagus. Thermal (recirculating a heated solution through the balloon), mechanical (increasing balloon volume), electrical (2 stimulation electrodes) and chemical sensitivity (modified Bernstein) were tested. Perception scores were evaluated on Visual Analogue Scales (VAS). Stimulus intensities were evaluated for first perception (VAS 1), pain perception threshold (VAS 5) and pain toleration threshold (VAS 7). General mood was assessed by the Positive and Negative Affect Schedule (PANAS) and the State-Trait Anxiety Inventory (STAI-state) questionnaires before and after the stimulations. Results were analyzed using repeated measures ANOVA or the non-parametric Kruskal-Wallis test. P-values of <0.05 were considered significant.
Results:Both naloxone and methylnaltrexone had no significant influence on esophageal sensitivity compared to placebo conditions. First perception, VAS 5 and VAS 7 thresholds did not differ when comparing naloxone or methylnaltrexone with placebo conditions during all stimulations. There was no difference for PANAS and STAI-State questionnaires before and after the stimulations for the different sessions.
Discussion:To our knowledge, this is the first study to address the role of endogenous opioids in determining esophageal sensitivity in health. We found no evidence of a tonic inhibitory effect of endogenous opioid pathways on esophageal sensitivity in health. The mechanisms of esophageal visceral pain perception are independent of endogenous opioid release.