Gastroenterology

Gastroenterology

Volume 134, Issue 7, June 2008, Pages 2070-2079
Gastroenterology

Basic–Alimentary Tract
A Rat Model of Chronic Gastric Sensorimotor Dysfunction Resulting From Transient Neonatal Gastric Irritation

https://doi.org/10.1053/j.gastro.2008.02.093Get rights and content

Background & Aims: Although several pathophysiologic abnormalities have been noted in functional dyspepsia (FD), their pathogenesis is poorly understood. We hypothesized that chronic gastric hypersensitivity and gastric motor dysfunction seen in FD patients can be modeled in rats by transient gastric irritation during the neonatal period, a time of known neuronal vulnerability to long-term plasticity. Methods: Ten-day-old male rats received 0.2 mL 0.1% iodoacetamide (IA) in 2% sucrose daily by oral gavages for 6 days; controls received 2% sucrose. Rats in both groups were then followed to adulthood (8–10 weeks) at which point behavioral, visceromotor, and great splanchnic nerve responses to graded gastric balloon distention (GD; 20–80 mm Hg) and gastric motor function were tested. Results: IA-treated rats exhibited hypersensitivity to GD in a dose-dependent manner, as compared with the control group. The threshold of afferent nerve activation was lower and nerve responses to GD were significantly increased in IA-treated rats. Although IA-treated rats ingested food at a lower rate, gastric emptying was not significantly different between IA and control groups. However, gastric accommodation was significantly reduced in the IA group. No significant gastric pathology was seen in hypersensitive adult rats compared with controls. Conclusions: These studies demonstrate that gastric irritation in the neonatal period can result in chronic gastric hypersensitivity and gastric motor dysfunction in adults even in the absence of significant detectable gastric pathology. Our results offer insight into the pathogenesis of chronic functional dyspepsia and provide a potential model for further study to this important clinical problem.

Section snippets

Animals

Male Sprague-Dawley rats were used in all the experiments (Harlan, Indianapolis, IN). The animal protocol was approved by the Institutional Animal Care and Use Committee of the University of Texas Medical Branch.

Neonatal Gastric Irritation

Ten-day-old rat pups received 0.2 mL of 0.1% iodoacetamide (IA) in 2% sucrose daily for 6 days by oral gavages. The control group received 0.2 mL of 2% sucrose.

Implantation of Balloon and Electrodes for Behavior and Electromyographic Testing

After overnight fasting, 8-week-old rats were anesthetized with intraperitoneal ketamine (60 mg/kg) and xylazine (7 mg/kg).

Neonatal IA Treatment Does Not Cause Long-Term Changes in Body Weight

Body weight was determined on days 2, 3, 4, 5, and 6 during 0.1% IA in 2% sucrose or 2% sucrose treatment and on day 18 post-treatment. Weight gain was significantly lower in the IA-treated rats during days 3–6 of the treatment period (*P < .05, Figure 1). However, by day 18, body weights in both groups were similar.

Neonatal IA Treatment Causes Mild and Transient Superficial Mucosal Injury

Gastric histology in neonatal rats 6 days following exposure to IA or sucrose (n = 8 in each group) revealed only superficial sloughing of the mucosa in the IA group without any

Discussion

In the current study, a sulfhydryl acetylating agent, IA, was used to induce a transient mild gastric inflammation in neonatal rats. This is based on reports that 0.1% IA for 5–7 days in adult rats or mice induces mild gastritis.16, 17, 18, 19 Furthermore, IA has been shown to result in acute changes of gastric sensory and motor function.8, 20 Our study showed that treatment with 0.1% IA orally once daily for 6 days in neonates induced mild but transient damage to the surface epithelium of

References (43)

Cited by (0)

Conflicts of interest: No conflicts of interest exist, and no potential investigator conflicts of interest exist.

View full text