Chronic stress induces hypersensitivity of murine gastric vagal afferents

Background: 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. Methods: 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.