A Rat Model of Chronic Gastric Sensorimotor Dysfunction Resulting From Transient Neonatal Gastric Irritation

Lian Sheng Liu, John Winston, Mohan M. Shenoy, Geng Qing Song, Jiande D Z Chen, Pankaj Jay Pasricha

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2070-2079
Number of pages10
JournalGastroenterology
Volume134
Issue number7
DOIs
StatePublished - Jun 2008

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Stomach
Iodoacetamide
Dyspepsia
Hypersensitivity
Sucrose
Gastric Balloon
Pathology
Splanchnic Nerves
Control Groups
Gastric Emptying
Food

ASJC Scopus subject areas

  • Gastroenterology

Cite this

A Rat Model of Chronic Gastric Sensorimotor Dysfunction Resulting From Transient Neonatal Gastric Irritation. / Liu, Lian Sheng; Winston, John; Shenoy, Mohan M.; Song, Geng Qing; Chen, Jiande D Z; Pasricha, Pankaj Jay.

In: Gastroenterology, Vol. 134, No. 7, 06.2008, p. 2070-2079.

Research output: Contribution to journalArticle

Liu, Lian Sheng ; Winston, John ; Shenoy, Mohan M. ; Song, Geng Qing ; Chen, Jiande D Z ; Pasricha, Pankaj Jay. / A Rat Model of Chronic Gastric Sensorimotor Dysfunction Resulting From Transient Neonatal Gastric Irritation. In: Gastroenterology. 2008 ; Vol. 134, No. 7. pp. 2070-2079.
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