STW 5 (Iberogast®) reduces afferent sensitivity in the rat small intestine

IntroductionA limited number of drugs are available for the treatment of functional dyspepsia and irritable bowel syndrome. The efficacy of STW 5 (Iberogast®) was previously shown in clinical trials. Since visceral hypersensitivity seems to be the prime pathomechanism of functional gastro-intestinal disorders, the aim of this study was to explore whether STW 5 reduces intestinal afferent sensitivity in the upper gastrointestinal tract.MethodsTwo groups of male Wistar rats were pretreated with either the herbal preparation STW 5 or its vehicle (30.8% ethanol). Then, after 2 h, general anesthesia was induced by pentobarbitone (60 mg kg−1 i.p.) and extracellular multi-unit afferent recordings were obtained from mesenteric afferents innervating the proximal jejunum. The intestinal afferent nerve response to increasing doses of 5-HT and bradykinin were quantified as well as afferent discharge following a ramp distension of the adjacent intestinal loop from 0 to 60 cm H2O.ResultsAfferent discharge to 5-HT and bradykinin increased dose-dependently. Following the different doses of 5-HT, the peak in afferent nerve discharge was always reduced after pretreatment with STW 5 compared to controls with a response of 110±5 imp s−1 after STW 5 and 128±3 in vehicle controls at the maximum dose (40 μg kg−1; p<0.05p<0.05; mean±SEM). For bradykinin, afferent responses were reduced following STW 5 at the 20 and 40 μg kg−1 dose but not at 10 μg kg−1 (40 μg kg−1: 176±7 imp s−1 following STW 5 versus 200±6 imp s−1 in controls; p<0.05p<0.05). The ramp distension of the intestinal loop stimulated a rise in intestinal afferent nerve discharge that was always lower in the STW 5 pretreated group compared to vehicle controls with the exception of the discharge rate at the pressure level of 0 and 20 cm H2O (all other pressures up to 60 cm H2O p<0.05p<0.05).ConclusionsSensitivity of intestinal afferents to mechanical and chemical stimuli is reduced following treatment with the herbal preparation STW 5. This mechanism may help to explain why STW 5 relieves dyspeptic and bowel symptoms in patients.