Randomised clinical trial: pregabalin attenuates the development of acid‐induced oesophageal hypersensitivity in healthy volunteers – a placebo‐controlled study

Abstract

SUMMARY BackgroundAcid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown.

Acid infusion into the esophagus increases the number of meal‐induced transient lower esophageal sphincter relaxations (TLESRs) in healthy volunteers

“…The infusion tube was connected to a peristaltic pump (flow rate 8 mL/min resulting in total volume of 160 mL during 20 min of infusion, pump type PCD 21M, Kouril, Czech Republic). The acidity, rate and duration of acid infusion were selected based on the thorough studies of acid‐induced central sensitization of esophageal pain threshold . We selected water over buffered saline (pH = 7) because a buffered solution would exert additional effects by buffering the acidity in the stomach.…”

Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity

“…Previously, we have developed and validated a human model of oesophageal pain hypersensitivity where following acid infusion into the distal oesophagus, pain thresholds (PTs) to electrical stimulation in the non-acid exposed proximal oesophagus are reduced due to central sensitisation 7. However, not all individuals who are exposed to this paradigm develop sensitisation, defined as less than 6 mA drop in PT to electrical stimulation, thus suggesting the presence of inter-individual factors that mediate postacidification gut sensitisation 8. These factors are incompletely defined and understood but a plausible postulation centres on the involvement of physiological aspects 9.…”

Evidence of a role for GTP cyclohydrolase‐1 in visceral pain

“…Next we evaluated the potential contribution of the pain protective GCH‐1 haplotype to visceral pain thresholds, and depression and anxiety scores, in healthy volunteers who were subjected to psychological profiling and esophageal pain testing using a previously well validated model of acid induced central sensitization . The study was approved by the local ethics committee and in accordance with GSK policy POL‐GSKF‐410.…”