A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation.
OBJECTIVE
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.
Liu
Lian-Sheng
LS
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5187, USA.
Winston
John H
JH
Shenoy
Mohan M
MM
Song
Geng-Qing
GQ
Chen
Jiande D Z
JD
Pasricha
Pankaj Jay
PJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001835:Body Weight; D002404:Catheterization; D002908:Chronic Disease; D004195:Disease Models, Animal; D004415:Dyspepsia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004435:Eating; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000294:innervation / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007460:Iodoacetamide; D008297:Male; D009043:Motor Activity; D009130:Muscle, Smooth / Q000294:innervation*; D009473:Neuronal Plasticity; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012678:Sensation Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012684:Sensory Thresholds; D013153:Splanchnic Nerves / Q000503:physiopathology*; D013270:Stomach / Q000294:innervation* / Q000473:pathology
D007460:Iodoacetamide