Influence of a herbal fixed combination preparation on intestinal afferent nerve sensitivity in a pharmacological in vivo model

An important factor in the pathophysiology of functional gastro-intestinal disorders seems to be visceral afferent sensitivity. The clinically proven herbal preparation STW 5 [1] containing 9 different extracts reduces intestinal afferent nerve sensitivity to different mechanical and chemical stimuli [2]. We aimed to determine whether the clinically proven herbal preparation STW 5-N II, containing 6 of the extracts from STW 5, but in a different composition [3], also reduces sensitivity to intestinal afferents.

The preparation STW 5-N II or vehicle were administered orally to male Wistar rats (250–350g) at a dose of 2.5, 5 or 10ml/kg (n=6–7 per group, gavage volume always 10ml/kg). Two hours later, animals were anesthetized (pentobarbitone 60mg/kg, i.p.) and extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum. Afferent discharge to luminal distension (0–60cm H₂O), bradykinin (15, 30 and 60µg/kg, i.v.) and 5-HT (5, 10, 20 and 40µg/kg, i.v.) were recorded. Peak discharge frequency was analyzed by two-way ANOVA.

At baseline, spontaneous afferent nerve discharge was not different following pretreatment with the various doses of STW 5-N II compared to vehicle. Afferent nerve sensitivity to bradykinin but not to 5-HT was significantly different depending on the dose of pretreatment with STW 5 N-II. After the highest oral dose (10ml), afferent discharge to bradykinin was 106±19, 153±22, and 156±25 (mean±SEM) compared to 160±15, 228±14 and 221±16 imp/s following vehicle pretreatment (p<0.05 for both, dose of bradykinin and STW 5-N II-dose). A pressure-dependent increase in afferent nerve discharge was observed during intraluminal distension that was not different following pretreatment with any dose of STW 5-N II.

The herbal preparation STW 5-N II desensitized intestinal afferents selectively to systemic bradykinin, which is a key mediator for pain perception. The different composition of this preparation may account for its more focussed action in comparison to the previously investigated STW 5. STW 5-N II may have a beneficial effect in patients suffering from disorders associated with visceral hypersensitivity.

[1] Rösch W et al.: Phytomedicine 2006; 13 SV: 114–121.

[2] Madisch A et al.: Digestion 2004; 69: 45–52.

[3] Liu CY et al.: Neurogastroent Motil 2004; 16: 759–764.