The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia

Abstract

An unidentified cause of functional dyspepsia (FD) is closely associated with medication resistance. Acid suppression is a traditional and preferential method for the treatment of FD, but the efficacy of this treatment varies between epigastric pain syndrome (EPS) and postprandial syndrome (PDS): it is efficient in the former but not much in the latter. Transepithelial electrical resistance (TEER), a surrogate of mucosal barrier function, was measured under pH 3 and pH 5 acidic conditions using duodenal biopsy specimens obtained from the patients with EPS and PDS and asymptomatic healthy controls. The infiltration of inflammatory cells to the duodenal mucosa was accessed by immunohistochemical analysis. The duodenal mucosal TEER in EPS patients was decreased by exposure to the acidic solution compared to that of the controls and the PDS patients. The decrease in TEER of the EPS patients was observed even under pH 5 weak acidic condition and was correlated to degree of the epigastric pain. Moreover, the duodenal mucosa of EPS patients presented an increase in mast cells and plasma cells that expressed Ig-E. Duodenal mucosal vulnerability to acid is likely to develop EPS.

Keywords: acid; duodenal mucosa; epigastric pain syndrome; mucosal vulnerability; transepithelial electrical resistance.

Figure 1

Transepithelial electrical resistance (TEER) in the duodenal mucosa. The exposure to a pH 3 or pH 5 acid solution was performed in each biopsy sample collected from the duodenal mucosa for 120 min during TEER measurements using a mini-Ussing chamber. Changes in the TEER are expressed as percentages relative to the initial values. Each plotted data point represents the mean ± standard deviation. (a) TEER in the controls (n = 23); (b) TEER in the EPS patients (n = 16); (c) TEER in the PDS patients (n = 11). Closed circle: the exposure to pH3 acidic solution, open square: the exposure to pH5 acidic solution. TEER: transepithelial electrical resistance, EPS: epigastric pain syndrome, PDS: postprandial distress syndrome. * p < 0.05, significant difference at each time point using Student’s t-test.

Figure 2

The changes of duodenal TEER in the different acidity of the exposure. Changes in the TEER are expressed as percentages relative to the initial values. Each plotted data point represents the mean ± standard deviation. (a) The duodenal TEER with the exposure to pH3 acid solution. (b) The duodenal TEER with the exposure to pH5 acid solution. Black circle and line: the healthy controls (n = 23), red triangle and dashed line: the EPS patients (n = 16), blue square and dotted line: the PDS patients (n = 11). TEER: transepithelial electrical resistance, EPS: epigastric pain syndrome, PDS: postprandial distress syndrome. p < 0.05, significant difference at each time point using Tukey–Kramer test; *, control vs. EPS; †, PDS vs. EPS.

Figure 3

Infiltration of immune cells in duodenal mucosa. Duodenal biopsy specimens obtained from the EPS and PDS patients, and the healthy controls were stained immunohistochemically for mast cell using tryptase antibody (a), eosinophils using eosinophilic MBP antibody (b) and Ig-E in plasma cells using Ig-E (c). The immunostaining of each antibody was quantified by counting on 3 randomly selected high-power fields for each sample (×400 magnification) (d,e). The number of Ig-E-positive cells was counted within the cells that were stained with CD138, comparing with serial sections of each staining (f). The immune-positive cells were counted in 3 randomly selected high-power fields on each sample (controls: n = 23, EPS patients: n = 16, PDS patients: n = 11). EPS: epigastric pain syndrome, PDS: postprandial distress syndrome, MBP: major basic protein. * p < 0.05, Tukey–Kramer test, NS: not significant, Bar indicates 20 μm.