Chronic stress induces hypersensitivity of murine gastric vagal afferents

Hui Li, Femke T.A. Buisman-Pijlman, Maria Nunez-Salces, Stewart Christie, Claudine L. Frisby, Antonio Inserra, George Hatzinikolas, Martin D. Lewis, Stamatiki Kritas, Ma Li Wong, Amanda J. Page

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)



Stress exposure is known to trigger and exacerbate functional dyspepsia (FD) symptoms. Increased gastric sensitivity to food‐related stimuli is widely observed in FD patients and is associated with stress and psychological disorders. The mechanisms underlying the hypersensitivity are not clear. Gastric vagal afferents (GVAs) play an important role in sensing meal‐related mechanical stimulation to modulate gastrointestinal function and food intake. This study aimed to determine whether GVAs display hypersensitivity after chronic stress, and whether its interaction with leptin was altered by stress.

Eight‐week‐old male C57BL/6 mice were exposed to unpredictable chronic mild stress or no stress (control) for 8 weeks. The metabolic rate, gastric emptying rate, and anxiety‐ and depression‐like behaviors were determined. GVA mechanosensitivity, and its modulation by leptin, was determined using an in vitro single fiber recording technique. QRT‐PCR was used to establish the levels of leptin and leptin receptor mRNA in the stomach and nodose ganglion, respectively.
Key Results

The stressed mice had lower body weight and food intake, and increased anxiety‐like behavior compared to the control mice. The mechanosensitivity of mucosal and tension‐sensitive GVAs was higher in the stressed mice. Leptin potentiated mucosal GVA mechanosensitivity in control but not stressed mice. The expression of leptin mRNA in the gastric mucosa was lower in the stressed mice.
Conclusions and Inferences

In conclusion, chronic stress enhances GVA mechanosensitivity, which may contribute to the gastric hypersensitivity in FD. In addition, the modulatory effect of leptin on GVA signaling is lost after chronic stress exposure.
Original languageEnglish
Article numbere13669
Number of pages10
JournalNeurogastroenterology and Motility
Issue number12
Early online date26 Jun 2019
Publication statusPublished - Dec 2019


  • chronic stress
  • functional dyspepsia
  • gastric hypersensitivity
  • gastric vagal afferents
  • leptin


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