Gastric administration of garlic powder containing the trpa1- agonist allicin induces specific epigastric symptoms and gastric relaxation in healthy subjects.

BACKGROUND: TRPA1 is an excitatory ion channel and is involved in sensory processes including thermal nociception and inflammatory pain. The allicin in garlic is a strong activator of the TRPA1 channel. AIM: To evaluate the effect of intragastric garlic powder containing allicin on perception, gastric tone, and mechanosensitivity. METHODS: An infusion-barostat balloon assembly was used for infusion of test solutions, for distension, and to measure proximal gastric compliance and tone. After an initial open label dose finding with 1 g, 2 g, 3.75 g, and 7.5 g commercially available garlic powder, a bolus of 2 g garlic powder (11 mg allicin)/60 mL H2 O was considered to induce moderate but constant sensation and was used hereafter in a placebo-controlled, single-dose, double-blind, randomized study in 7 volunteers to evaluate gastric sensation, tone, and mechanosensitivity. KEY RESULTS: Bolus injection of garlic caused immediate epigastric symptoms, mean aggregate symptom scores (AUC in 15 minutes) were 106 ± 49 vs. 35 ± 30 after placebo (P = 0.01). Garlic induced significant epigastric pressure, stinging, and warmth (P < 0.01 vs. placebo), while intensity of cramps, satiety, nausea, and pain was not significantly different to placebo (P > 0.05). Garlic induced an immediate, short lived fundic relaxation (balloon volume 627 ± 349 mL vs. -145 ± 120 mL; P < 0.02). No effect of allicin on proximal gastric mechanosensitivity and compliance was observed (NS). CONCLUSION AND INFERENCES: Garlic containing allicin induces immediate epigastric symptoms of pressure, stinging, and warmth and induces fundic relaxation but does not influence mechanosensitivity or compliance. TRPA1 is a receptor that is involved in gastric sensation and motility.

Lack of an Effect of Gastric Capsaicin on the Rectal Component of the Gastrocolonic Response.

Luminal capsaicin induces local and distant reflexes in the upper gastrointestinal tract and stimulates lower gastrointestinal symptoms in susceptible persons. We aimed to evaluate the effect of gastric capsaicin on rectal motor function and sensation. METHODS: Eighteen healthy volunteers participated twice, at least 1 week apart, in this double-blind, placebo-controlled crossover study. Participants swallowed a gastric tube for capsaicin or saline infusion. A barostat tube was placed in the rectum to measure rectal tone before and during gastric capsaicin (40 µg/ml, 2.5 ml/min) or placebo infusion and to conduct distension experiments before and after gastric infusions. Gastric infusions were terminated after 60 min or when epigastric discomfort occurred. Differences in rectal tone, compliance, and sensitivity between gastric placebo and gastric capsaicin were determined. RESULTS: On both study days, basal rectal volumes, compliance, and sensitivity parameters were comparable (NS) before gastric infusions. Gastric capsaicin infusion induced epigastric discomfort that necessitated termination of infusion after 29.6 ± 12.3 min (saline: 54.7 ± 8.9 min; p < 0.01). Rectal tone, aggregate perception scores, and rectal compliance did not differ between placebo and capsaicin trials (p > 0.05). Rectal tone increased significantly only when capsaicin induced epigastric discomfort (p < 0.05). The reproducibility of the barostat trial was acceptable with significant correlations of volumes, pressures (< 0.05; r 2 from 0.41 to 0.55), rectal compliance (p < 0.01; r 2 = 0.44), and aggregate perception scores (p values all < 0.05; r 2 from 0.44 to 0.0.65) between the two barostat trials. CONCLUSION: Gastric perfusion with capsaicin does not directly influence rectal physiology through a reflex arc.

Long-term success of GUT-directed group hypnosis for patients with refractory irritable bowel syndrome: a randomized controlled trial.

OBJECTIVES: Gut-directed hypnotherapy (GHT) in individual sessions is highly effective in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the long-term effect of GHT in group sessions for refractory IBS. METHODS: A total of 164 patients with IBS (Rome-III-criteria) were screened, and 100 refractory to usual treatment were randomized 1:1 either to supportive talks with medical treatment (SMT) or to SMT with GHT (10 weekly sessions within 12 weeks). The primary end point was a clinically important improvement on several dimensions of daily life (assessed by IBS impact scale) after treatment and 12-month follow-up. The secondary end point was improvement in general quality of life (QOL; Medical Outcome Study Short-Form-36), psychological status (Hospital Anxiety Depression Scale) and reduction of single IBS symptoms. Analysis was by intention to treat. RESULTS: A total of 90 patients received allocated intervention. After treatment, 28 (60.8%) out of 46 GHT patients and 18 (40.9%) out of 44 SMTs improved (absolute difference 20.0%; 95% confidence interval (CI): 0-40.2%; P=0.046); over 15 months, 54.3% of GHT patients and 25.0% of controls improved (absolute difference 29.4%; 95% CI 10.1-48.6%; P=0.004). GHT with SMT improved physical and psychological well being significantly more than SMT alone (P<0.001). Gender, age, disease duration and IBS type did not have an influence on the long-term success of GHT. CONCLUSIONS: GHT improves IBS-related QOL, is superior to SMT alone, and shows a long-term effect even in refractory IBS.

Duodenal chemosensitivity and mechanosensitivity in humans during acid and ethanol perfusion.

INTRODUCTION: Chemical stimulation with capsaicin in the intestinal lumen induces abdominal pain, presumably through a mechanism involving the polymodal vanilloid receptor TRPV1 (transient receptor potential vanilloid receptor subtype 1). Other stimulators of TRPV1 include heat, acid or ethanol. We evaluated the effects of duodenal acid and ethanol exposure on chemosensitivity and mechanosensitivity in healthy volunteers. METHODS: In two placebo-controlled arms of the study, healthy volunteers received duodenal infusions of either hydrochloric acid (0.1 mol/l) (n=8) or ethanol (5% vol/vol) through an oroduodenal tube. Mechanosensitivity was tested applying pressure-controlled duodenal distensions and chemosensitivity was tested by duodenal perfusion with capsaicin (40 microg/ml; 2.5 ml/min). Quality and intensity of upper abdominal symptoms were evaluated with a graded questionnaire during mechanical and chemical stimulation of the duodenum. RESULTS: During hydrochloric acid infusion, capsaicin-induced perception was reduced (P<0.01) and latency to discomfort was increased from 24.5 min (25th/75th%:16.5/36 min) during placebo to 50 min (25.5/60 min) (P<0.01). Ethanol had no significant effect on chemosensitivity [latency to discomfort for placebo vs. ethanol: 26 min (18/40 min) vs. 20 min (9/60 min)] (P>0.05). Neither duodenal acidification nor ethanol altered mechanosensitivity significantly (P>0.05). CONCLUSION: Duodenal acid activated mechanisms that lead to a decreased sensitivity for intraluminal capsaicin; these mechanisms might protect duodenal chemonociceptors from being sensitized by acid. Whether this mechanism is impaired in patients with upper gastrointestinal functional disease remains to be determined.