The Effect of Naloxone and Mehtylnaltrexone on Esophageal Sensitivity in Healthy Volunteers: a Randomized, Double-blind, Placebo-controlled Study

INTRODUCTION Gastroesophageal reflux disease (GERD), defined as the presence of symptoms or lesions that can be attributed to the reflux of gastric contents into the esophagus, is an increasingly prevalent condition in Western societies. The most typical symptoms are heartburn and regurgitation, but GERD can manifest itself through a variety of esophageal and extra-esophageal symptoms (e.g. chronic cough).

In humans, pain is a multimodal experience composted of sensory, physiological and psychological aspects. In order to mimic the clinical situation, experimental models should be based on multimodal testing regimens in which different receptors and central nervous system mechanisms are activated.

Advances in esophageal sensory stimulation have established that both typical and atypical symptoms may not only arise from acid reflux, but also from reflux events with less acidic pH (pH 4-7). In GERD patients with symptoms that persist in spite of PPIs, ongoing weakly acidic reflux is now well established as the main underlying factor.

The basis for symptom generation during weakly-acidic reflux events remains to be determined, but acid sensitivity in the pH range 4-7, mechanical distention (enhanced by air in the refluxate), sensitivity to other chemical factors (e.g. bile) and esophageal hypersensitivity to physiological levels of reflux have all been proposed.

HYPOTHESIS The investigators speculated that visceral hypersensitivity plays an important role in symptom perception. This is suggested by the reflux parameters that are usual within the physiological number during PPI therapy.