Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model.
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 < or = 0.0001). In study 2, increasing acid concentrations had a significant effect over multiple time points, P < or = 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.
Matthews
Philip J
PJ
Institute of Cellular and Molecular Science, Barts and the London, Queen Mary's School of Medicine and Dentistry, Whitechapel, London, UK
Knowles
Charles H
CH
Chua
Yang C
YC
Delaney
Claire
C
Hobson
Anthony R
AR
Aziz
Qasim
Q
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D005260:Female; D005764:Gastroesophageal Reflux / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage* / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017288:Pain Threshold; D013997:Time Factors
D006851:Hydrochloric Acid