Abstract
Psychological factors, especially stress, are known to play an important role in functional gastrointestinal diseases (1, 2). Based on the good correlation between stress and functional dyspepsia (FD), many animal models for FD have been developed where animals are subjected to psychological stress either during the neonatal period or in adulthood. This stress was found to induce gastric motor dysfunction resembling symptoms of FD. In one model, maternal separation (3) was performed on weanling rats starting from postnatal day 2 for 3h each day for 3 weeks. Rats were then allowed to mature to an adult age. The other model was that of restraint stress (RS) (4, 5). Adult animals were restrained for 90min/day for 1 week. The animals of both models were eventually sacrificed, the stomach fundus was isolated and its sensitivity in vitro to carbachol, potassium chloride, serotonin and adrenaline was tested. Blood samples were taken to assess levels of ghrelin, corticosterone releasing factor (CRF) and corticosterone. The sensitivity of fundus strips from restrained rats towards the agents tested, partly representing autonomic responsiveness, was more depressed than those from maternally separated ones. Levels of ghrelin, CRF and corticosterone were also more elevated in the RS model. That model was therefore chosen to test the efficacy of STW 5 in restoring the deranged parameters. A group of animals received STW 5 orally once daily starting treatment 1 week before exposing them to RS and continuing treatment for a further week during subjection to RS. STW 5 was effective in normalizing the depressed stomach fundus responses exhibited by animals subjected to RS and to normalize to a large extent the deranged blood levels of ghrelin, CRF and corticosterone. The findings lend further evidence to the role of the brain-gut axis in FD and gives supportive evidence for the first time for the clinical usefulness of STW 5 in this condition.
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