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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/G914    most recent 00445.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Matthews, P. J. Articles by Aziz, Q. Search for Related Content PubMed PubMed Citation Articles by Matthews, P. J. Articles by Aziz, Q.

NEUROREGULATION AND MOTILITY

Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model

¹Institute of Cellular and Molecular Science, Barts and the London, Queen Mary's School of Medicine and Dentistry, Whitechapel, London; ²Department of Gastrointestinal Science, Hope Hospital, Salford; ³Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development, Stevenage, United Kingdom

Submitted 28 September 2007 ; accepted in final form 1 February 2008

Previous studies have demonstrated that a single 30-min distal esophageal infusion of concentrated (0.15 M, pH 0.8) hydrochloric acid (HCl) induces hyperalgesia to an electrical stimulus in a human model. The aim of this study was to refine this model using physiological acid concentrations (pH 1.8–4) in repeated short exposures. Two different cohorts of 10 volunteers underwent two studies. Study 1: randomization to four 5-min distal esophageal infusions of acid (0.15 M) or saline, 1 h apart. Double-blind measurements of baseline and postexposure proximal esophageal and chest wall pain thresholds (PTs) were performed to electrical stimulation at 30-min intervals throughout the study. Study 2: randomization to four 15-min infusions of 0.15, 0.075, and 0.01 M HCl and saline. In study 1, with multiple acid infusions, a significant progressive drop in PTs was observed in both areas tested (P 0.0001). In study 2, increasing acid concentrations had a significant effect over multiple time points, P 0.0001. Similar initial reductions in PTs were observed for all acid concentrations compared with saline; however, hypersensitivity was shorter lasting with 0.01 M acid. In healthy subjects, esophageal hypersensitivity can be induced and maintained up to 4 h by repeated short-duration acid infusion and at physiological pH levels. This has implications for future model design and pathophysiological understanding of acid-related esophageal hypersensitivity.

central sensitization; gastroesophageal reflux disease; visceral hyperalgesia