Anti-nociceptive effect of STW 5-II in rodent models of stress and post-inflammatory visceral hypersensitivity

Abstract

Aims

Visceral hypersensitivity is a therapy-resistant hallmark of irritable bowel syndrome (IBS). Many IBS patients’ symptoms develop following an acute colitis, and most report that stress worsens symptoms. STW 5-II, a combination of six herbal extracts, is a clinically proven treatment for IBS, but the mechanism is uncertain. Here, we employ two well-characterized rodent models to test the hypothesis that STW 5-II attenuates chronic colonic hypersensitivity.

Main methods

Separate cohorts of male rats were used for each model of colonic hypersensitivity. The first model used repeated water avoidance stress (1hr/day for 10 days), while the second model used intracolonic trinitrobenzene sulfonic acid to induce a short-lived colitis followed by post-inflammatory visceral hypersensitivity. Both models used sham treatment controls. Colonic sensitivity was quantified as the number of abdominal contractions to graded pressures (20–60 mmHg) of isobaric colorectal distension (CRD). Phosphorylation of extracellular signal-regulated kinase (pERK) was assessed via immunohistochemistry in the brain, spinal cord, and dorsal root ganglion (DRG). STW 5-II (10 ml/kg, p.o.) or vehicle (p.o.) was administered for 7 days, prior to CRD and pERK expression.

Key findings

Rats exposed to either model developed significant colonic hypersensitivity. Both models enhanced CRD-evoked pERK in DRGs, spinal cord, and brain. STW 5-II decreased colonic hypersensitivity and reduced CRD-evoked brain, spinal, and DRG pERK.

Significance

Both models induced colonic hypersensitivity and enhanced pERK expression. STW 5-II inhibited colonic hypersensitivity and decreased noxious neuronal activation in both models, which could explain its clinically proven efficacy in relieving visceral hypersensitivity-related symptoms in IBS.