Oesophageal afferent pathway sensitivity in non-erosive reflux disease

Patients with non-erosive reflux disease (NERD) report symptoms which commonly fail to improve on conventional antireflux therapies. Oesophageal visceral hyperalgaesia may contribute to symptom generation in NERD and we explore this hypothesis using oesophageal evoked potentials. Fifteen endoscopically confirmed NERD patients (four female, 29-56 years) plus 15 matched healthy volunteers (four female, 23-56 years) were studied. All patients had oesophageal manometry/24-h pH monitoring and all subjects underwent evoked potential and sensory testing, using electrical stimulation of the distal oesophagus. Cumulatively, NERD patients had higher sensory thresholds and increased evoked potential latencies when compared to controls (P = 0.01). In NERD patients, there was a correlation between pain threshold and acid exposure as determined by DeMeester score (r = 0.63, P = 0.02), with increased oesophageal sensitivity being associated with lower DeMeester score. Reflux negative patients had lower pain thresholds when compared to both reflux positive patients and controls. Evoked potentials were normal in reflux negative patients but significantly delayed in the reflux positive group (P = 0.01). We demonstrate that NERD patients form a continuum of oesophageal afferent sensitivity with a correlation between the degree of acid exposure and oesophageal pain thresholds. We provide objective evidence that increased oesophageal pain sensitivity in reflux negative NERD is associated with heightened afferent sensitivity as normal latency evoked potential responses could be elicited with reduced afferent input. Increased oesophageal afferent pain sensitivity may play an important role in a subset of NERD and could offer an alternate therapeutic target.