Abstract

Background The role of protease-activated receptor 2 (PAR2) in the analgesic effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in postinfectious irritable bowel syndrome (PI-IBS) has yet to be elucidated. Aim In this study, we investigated the molecular mechanisms underlying the analgesic effect of EA in a rat model of PI-IBS. Methods Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex test before and after administration of the PAR2 agonist, PAR2-AP, and/or EA. The protein expression and mRNA levels of PAR2, CGRP, SP, and TPSP in colon tissues were measured by immunofluorescence, western blot, and RT-PCR. Results We found that EA could alleviate VH and significantly decrease protein and mRNA levels of PAR2, TPSP, CGRP, and SP in PI-IBS rats. The analgesic effect of EA on VH was slightly reduced in the presence of PAR2-AP. Conclusions These results suggest that EA alleviates VH symptoms through downregulation of the levels of the TPSP/PAR2/SP/CGRP signaling axis in colon tissues in PI-IBS rats. Together, our data suggests that PAR2 plays a critical role in the analgesic effect of EA on VH in PI-IBS.

Highlights

  • Irritable bowel syndrome (IBS) is a common, chronic, functional gastrointestinal disorder, characterized by visceral hypersensitivity (VH) or abdominal discomfort, as well as altered bowel habits, without obvious anatomical or biochemical abnormalities

  • We focused our attention on protease-activated receptor 2 (PAR2), since it has been shown to cause VH symptoms in postinfectious irritable bowel syndrome (PI-IBS) rats, and we investigated tryptase (TPSP), which is upstream of PAR2, as well as substance P (SP) and calcitonin generelated peptide (CGRP) which are regarded as secondary neurotransmitters in colon tissues

  • Our results show that EA alleviates VH symptoms by downregulating the levels of PAR2 and TPSP, a protein upstream of PAR2, as well as the levels of the secondary neurotransmitters SP and CGRP in colon tissues in PI-IBS rats

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Summary

Introduction

Irritable bowel syndrome (IBS) is a common, chronic, functional gastrointestinal disorder, characterized by visceral hypersensitivity (VH) or abdominal discomfort, as well as altered bowel habits, without obvious anatomical or biochemical abnormalities. The role of protease-activated receptor 2 (PAR2) in the analgesic effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in postinfectious irritable bowel syndrome (PI-IBS) has yet to be elucidated. The protein expression and mRNA levels of PAR2, CGRP, SP, and TPSP in colon tissues were measured by immunofluorescence, western blot, and RT-PCR. We found that EA could alleviate VH and significantly decrease protein and mRNA levels of PAR2, TPSP, CGRP, and SP in PI-IBS rats. These results suggest that EA alleviates VH symptoms through downregulation of the levels of the TPSP/PAR2/SP/CGRP signaling axis in colon tissues in PI-IBS rats. Our data suggests that PAR2 plays a critical role in the analgesic effect of EA on VH in PI-IBS

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