title: Development of esophageal hypersensitivity following experimental duodenal acidification.
abstract: OBJECTIVE
  As visceral afferents from different regions of the gastrointestinal tract converge at the level of the spinal cord, we hypothesized that sensitization of one gut organ would induce visceral hypersensitivity in another gut organ, remote to the sensitizing stimulus.
  
  
  METHODS
  Protocol 1: Eight healthy male volunteers, age 30 +/- 8.2 yr, underwent three studies on different days. Esophageal pain thresholds (PT) were recorded at 10-min intervals prior to and for 2 h following a 30-min duodenal infusion of either 0.15 M hydrochloric acid (HCl), saline, or no infusion. Five subjects repeated the study to demonstrate reproducibility. Protocol 2: Esophageal evoked potentials (EEP) were studied in six subjects on two occasions prior to and 1 h after a 30-min duodenal infusion of 0.15 M HCl or saline.
  
  
  RESULTS
  Protocol 1: After acid infusion, there were reproducible reductions in esophageal PT (ICC = 0.88), which were maximal at 110 min (15.05 +/- 2.25 mA) (p < 0.002). Following saline infusion there was an increase in esophageal PT (ICC = 0.71), which was similar to the no-infusion condition (6.21 +/- 1.54 mA vs 8.5 + 7.6 mA; p > 0.05). Protocol 2: Esophageal sensation scores increased (p= 0.02) after acid, but not after saline infusion (p= 0.1). A comparison of the latencies of EEP components prior to and following acid and saline infusion revealed a reduction in the N1 (p= 0.02) and P2 components (p= 0.04).
  
  
  CONCLUSIONS
  This study provides the first objective evidence that duodenal acidification can induce esophageal hypersensitivity associated with changes in sensitivity of the central visceral pain pathway. As the esophagus was remote from the sensitizing stimulus, central sensitization of spinal dorsal horn neurons is likely to have contributed to these changes.
authors.affiliation: Section of Gastrointestinal Sciences, University of Manchester, Hope Hospital, Salford, United Kingdom.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Hobson
authors.forename: Radia W
authors.initials: RW
authors.lastname: Khan
authors.forename: Sanchoy
authors.initials: S
authors.lastname: Sarkar
authors.forename: Paul L
authors.initials: PL
authors.lastname: Furlong
authors.forename: Qasim
authors.initials: Q
authors.lastname: Aziz
mesh_terms: D000328:Adult; D004386:Duodenum / Q000187:drug effects*; D004947:Esophagus / Q000187:drug effects* / Q000503:physiopathology*; D005744:Gastric Acid; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D006941:Hyperesthesia / Q000139:chemically induced / Q000503:physiopathology; D007419:Intestinal Secretions / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D006851:Hydrochloric Acid