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Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
  1. Ricard Farré1,
  2. Rita De Vos2,
  3. Karel Geboes2,
  4. Kristine Verbecke3,
  5. Pieter Vanden Berghe1,
  6. Inge Depoortere1,
  7. Kathleen Blondeau1,
  8. Jan Tack1,
  9. Daniel Sifrim1
  1. 1Center for Gastroenterological Research, Catholic University Leuven, Belgium
  2. 2Department of Pathology, University Hospital Gasthuisberg, Catholic University Leuven, Belgium
  3. 3Laboratory of Digestion and Absorption, University Hospital Gasthuisberg, Catholic University Leuven, Belgium
  1. Correspondence to:
    Professor Daniel Sifrim
    Faculty of Medicine, KU Leuven, Lab G-I Physiopathology, O & N Gasthuisberg, Herestraat 49, 7th floor, 3000 Leuven, Belgium; daniel.sifrim{at}


Background: In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces.

Methods: Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to 51Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy.

Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm2 vs 5.8±2.1 pmol/cm2) (p<0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin).

Conclusions: Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.

  • DIS, dilated intercellular spaces
  • GERD, gastroesophageal reflux disease
  • HPA, hypothalamic-pituitary-adrenal
  • KHBB, Krebs–Henseleit bicarbonate buffer
  • PRS, Partial Restraint Stress
  • TEM, transmission electron microscopy
  • stress
  • permeability
  • dilated intercellular spaces
  • rat
  • oesophageal mucosa

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  • Published Online First 1 February 2007

  • Statement of competing interests: None to declare.