Tu1448 Gabapentin/Pregabalin Improves Symptoms in Patients With Upper GI Functional Disease and Gut Dysmotility

Abstract

G A A b st ra ct s shown the GI pharmacological effects of allyl isothiocyanate (AITC), a pungent ingredient of wasabi and a TRPA1 channel activator. It was found that 1) AITC impairs tight junction barrier in primary cultures of rat stomachs (Capsaicin 2014, DOI: 10.5772/57289), and 2) no gastric damage by AITC was observed in ex-vivo rat stomachs (Gastroenterology, 138 (5), S-721, 2010). Therefore, this study is to establish a rodent model of impaired gastric motility resulting from gastric low-grade inflammation by AITC, which is reliable produce to evaluate therapeutic agents of FD. METHODS: Gastric low-grade inflammation: Male SD rats were used after 18 h-fasting. Stomachs mounted on ex-vivo chambers under urethaneanesthetized rats treated with omeprazole, were perfused with 50 mM HCl. Vascular permeability (Pontamine Sky blue) was measured during and 90 min after exposure to AITC (0.33~30 mM) for 30 min. A-967079 (10 mM), a TRPA1 channel blocker, was co-applied with AITC. Gastric motility: Male ddY mice were used after 15 h-fasting. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (1-100 mg/kg, p.o.) was given 30 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), and neostigmine (30 μg/kg), or a therapeutic agent for FD acotiamide (10, 30 mg/kg) was given s.c. 40 min before the measurement. RESULTS: Gastric low-grade inflammation: AITC increased vascular permeability in exvivo rat stomachs in concentration-dependent manner, which is obviously increased over 10 mM of AITC. However, increased vascular permeability induced by AITC was not inhibited by A-967079. Gastric motility: AITC (%30 mg/kg) impaired gastric motility in dose-dependent manner in conscious mice, those impaired motility was reversible to normal levels for 24 h after treatment of AITC. Decreased gastric motility induced by AITC (80 mg/ kg) was restored by the pretreatment of itopride, mosapride (1 mg/kg), or neostigmine. Acotiamide (100 mg/kg) also recovered decrease of gastric motility. Gastric macroscopic damage was not observed at the end of the experiments and 24 h after treatment of AITC (80 mg/kg). CONCLUSION: These results suggest that AITC induced gastric low-grade inflammation in the rodent stomach, which is independent on TRPA1 channels and no gastric mucosal damage. In addition, AITC produced the impaired gastric motility in conscious mice, whose phenomenon was reversible by prokinetic agents and a therapeutic agent for FD. This rodent model might be useful tool to develop new therapeutic agents for FD.