Abstract
Visceral hypersensitivity (VH) is the predominant pathogenesis of functional dyspepsia (FD). Duodenal hypersensitivity along with nausea further reduces the comfort level in gastric balloon dilatation and inhibits gastric receptive relaxation. The potential mechanism behind electroacupuncture- (EA-) mediated alleviation of VH has not been elucidated. In an FD rat model with tail clamping stress, iodine acetamide (IA) induced VH. The rats were treated with EA with or without PAR2 antagonist FSLLRY-NH2, and the body weight, gastric sensitivity, compliance, and gastrointestinal motility were determined. Mast cells and activated degranulation were stained with toluidine blue (TB) staining and visualized under a transmission electron microscope (TEM). Immunofluorescence was used to detect the expression of PAR2, PKC, and TRPV1 in the duodenum and dorsal root ganglion (DRG) and that of CGRP, SP in DRG, and c-fos in the spinal cord. EA alone and EA + antagonist enhanced the gastrointestinal motility but diminished the expression of TRPV1, CGRP, SP, and c-fos-downstream of PAR2/PKC pathway and alleviated VH in FD rats. However, there was no obvious superposition effect between the antagonists and EA + antagonists. The effect of EA alone was better than that of antagonists and EA + antagonists 2 alone. EA-induced amelioration of VH in FD rats was mediated by TRPV1 regulation through PAR2/PKC pathway. This protective mechanism involved several pathways and included several targets.
Highlights
Functional dyspepsia (FD), a common chronic gastrointestinal disease, is characterized by upper abdominal pain or burning sensation, postprandial fullness, early satiety, belching, and other symptoms [1]
According to the diagnostic criteria of Rome IV functional gastrointestinal diseases, FD was classified into two subgroups: epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) [2]. e global prevalence rate of FD is 21.8%, though there is a significant variation of this rate from country to country [3]
protease-activated receptor 2 (PAR2) and TRPV1 are colocalized in the primary afferent nerve and coexpressed in more than 60% of L4–6 dorsal root ganglion (DRG) cells, whereas both calcitonin gene-related peptide (CGRP) and SP are evident in 20% of the 35% PAR2-expressing neurons [9]
Summary
Functional dyspepsia (FD), a common chronic gastrointestinal disease, is characterized by upper abdominal pain or burning sensation, postprandial fullness, early satiety, belching, and other symptoms [1]. Ese neuropeptides increase VH and induce FD symptoms (including abdominal pain and nausea) [7]. Acupuncture has been explored as a potentially effective nondrug therapy for functional gastrointestinal diseases. High-quality RCT validated significant amendment with acupuncture thrice a week in the PDS symptoms of FD patients with improved quality of life. E present study employed iodine acetamide (IA) combined with tail clamping stress to induce the FD rat model and explored the effect of EA on intestinal hypersensitivity in FD rats to determine whether EA alleviated intestinal hypersensitivity through the PAR2/TRPV1 signal pathway Our previous studies reported that EA at the acupoints (“Zusanli” and “Taichong”) improved gastrointestinal motility and reduced low-grade duodenal inflammation in FD model rats [14, 15], substantiating the effectiveness of these two acupoints. e present study employed iodine acetamide (IA) combined with tail clamping stress to induce the FD rat model and explored the effect of EA on intestinal hypersensitivity in FD rats to determine whether EA alleviated intestinal hypersensitivity through the PAR2/TRPV1 signal pathway
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