Neonatal maternal separation followed by restraint stress as a sequential stress model for functional dyspepsia: Efficacy of the herbal preparation STW 5

Functional dyspepsia (FD) is one of the most common GI-disorders. Because of the chronic relapsing nature and lack of effective treatment options, FD is associated with significantly impaired quality of life and considerable costs. Based on the central role stress seems to be playing in functional GI-diseases, available animal models for FD rely on exposing animals to various types of stress. Clinical studies have shown that adverse physiological or psychological experiences in early life are associated with the development of FD symptoms, as well as acute stressful conditions in adulthood. Hence, childhood traumatic experiences followed by later exposure to acute stress may play key roles in the development and modulation/maintenance of FD. In the present study, we tried to mimic this situation by combining early life stress (neonatal maternal separation, NMS) and acute stress in adulthood (restraint stress, RS) in rats, in the hope of developing a multidimensional experimental model of FD with closer resemblance to clinical situation. To explore the validity of this sequential stress model, we tested the effects of STW5 as a standard drug. Fundus strips from rats subjected to the combined stress showed significantly reduced responses to adrenaline, carbachol, KCl and 5HT as compared to those from normal rats or animals subjected to either stressor. Animals treated with STW5 showed normalized response to adrenaline, carbachol and 5HT. Combined stress also markedly increased plasma levels of CRF to twice as much as either stressor alone as well as plasma corticosterone. STW5 protected against the increase in both CRF and corticosterone. These data indicate that combined early life stress and acute stress effectively induce stomach motility disorders as well as hormonal derangements that might be more representative of the complex clinical situation and might represent a model for the screening of new FD drugs. It could also illustrate some of the mechanisms of action of STW5 in FD.