The role of peripheral corticotropin-releasing factor signaling in a rat model of stress-induced gastric hyperalgesia

Background: Functional dyspepsia (FD) is a common gastrointestinal disorder associated with persistent or recurrent upper gastrointestinal tract symptoms such as pain without any obvious pathological changes. Psychological and psychiatric factors might have a pathogenic role in FD. Changes in the sensation of stomach pain were determined after application of stress to adult rats. The involvement of corticotropin-releasing factor (CRF), Type 2 CRF receptor (CRF₂) and inflammatory cytokine interleukin-6 (IL-6) was also investigated in the gastric hyperalgesia observed in this model.

Results: Repeated water avoidance stress (WA-S) produced gastric hyperalgesia, with no obvious lesions in the gastric mucosa. Gastric hyperalgesia was inhibited by CRF and CRF₂ antagonists, suggesting their involvement in gastric hyperalgesia observed after application of stress. Gastric hyperalgesia was inhibited by IL-6 neutralizing antibody. Immunofluorescence staining demonstrated CRF, CRF₂, urocortin (Ucn)1, and Ucn2-positive cells in the gastric mucosa. CRF₂-positive cells increased after WA-S, compared to sham stress. CRF₂ and Ucn2 were expressed in the mast cells in the gastric mucosa.

Conclusions: CRF₂ plays an important role in gastric hyperalgesia produced by stress. CRF₂ signaling may be a useful therapeutic target for functional dyspepsia.