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Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats

Background: Visceral hypersensitivity (VH) is one of the underlying pathophysiologies of irritable bowel syndrome. Mast cell overactivation has been found to be one of the main causes of VH. We investigated the effects and mechanisms of actions of sacral nerve stimulation (SNS) on visceral pain in a...

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Autores principales: Jin, Xue, Gharibani, Payam, Yin, Jieyun, Chen, Jiande D. Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282909/
https://www.ncbi.nlm.nih.gov/pubmed/34276280
http://dx.doi.org/10.3389/fnins.2021.645393
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author Jin, Xue
Gharibani, Payam
Yin, Jieyun
Chen, Jiande D. Z.
author_facet Jin, Xue
Gharibani, Payam
Yin, Jieyun
Chen, Jiande D. Z.
author_sort Jin, Xue
collection PubMed
description Background: Visceral hypersensitivity (VH) is one of the underlying pathophysiologies of irritable bowel syndrome. Mast cell overactivation has been found to be one of the main causes of VH. We investigated the effects and mechanisms of actions of sacral nerve stimulation (SNS) on visceral pain in a rodent model of VH. Methods: The VH was established by an intrarectal infusion of AA in 10-day-old pups. Rats were chronically implanted with electrodes for SNS and recording electromyogram (EMG) and electrocardiogram. The acute study was performed in 2-randomized sessions with SNS (14 Hz, 330 μs, 40% motor threshold or MT, 30 min) or sham-SNS. Later on, rats were randomized into SNS/sham-SNS groups and a chronic study was performed with 2 h-daily SNS or sham-SNS for 21 days. Visceromotor reflexes were assessed by abdominal EMG and withdrawal reflex (AWR). Colon tissues were collected to study colonic acetylcholine (ACh), the enteric neurons (ChAT, nNOS, and PGP9.5), mast cells activity [Tryptase, prostaglandins E2 (PGE2), and cyclooxygenases-2 (COX2)] and pain markers [nerve growth factor (NGF) and Sub-P]. Key Results: Sacral nerve stimulation significantly improved visceromotor reflexes assessed by the EMG and AWR, compared with sham-SNS. SNS normalized the protein expressions of ChAT and nNOS and regulated mast cells activity by downregulating Tryptase, COX2, and PGE2. Neonatal AA administration upregulated NGF and Sub-P; chronic SNS significantly decreased these pain biomarkers. Concurrently, chronic SNS increased ACh in colon tissues and vagal efferent activity. Conclusions: Sacral nerve stimulation reduces VH in rats and this ameliorating effect might be attributed to the suppression of mast cell overactivation in the colon tissue via the modulation of autonomic nervous system functions.
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spelling pubmed-82829092021-07-17 Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats Jin, Xue Gharibani, Payam Yin, Jieyun Chen, Jiande D. Z. Front Neurosci Neuroscience Background: Visceral hypersensitivity (VH) is one of the underlying pathophysiologies of irritable bowel syndrome. Mast cell overactivation has been found to be one of the main causes of VH. We investigated the effects and mechanisms of actions of sacral nerve stimulation (SNS) on visceral pain in a rodent model of VH. Methods: The VH was established by an intrarectal infusion of AA in 10-day-old pups. Rats were chronically implanted with electrodes for SNS and recording electromyogram (EMG) and electrocardiogram. The acute study was performed in 2-randomized sessions with SNS (14 Hz, 330 μs, 40% motor threshold or MT, 30 min) or sham-SNS. Later on, rats were randomized into SNS/sham-SNS groups and a chronic study was performed with 2 h-daily SNS or sham-SNS for 21 days. Visceromotor reflexes were assessed by abdominal EMG and withdrawal reflex (AWR). Colon tissues were collected to study colonic acetylcholine (ACh), the enteric neurons (ChAT, nNOS, and PGP9.5), mast cells activity [Tryptase, prostaglandins E2 (PGE2), and cyclooxygenases-2 (COX2)] and pain markers [nerve growth factor (NGF) and Sub-P]. Key Results: Sacral nerve stimulation significantly improved visceromotor reflexes assessed by the EMG and AWR, compared with sham-SNS. SNS normalized the protein expressions of ChAT and nNOS and regulated mast cells activity by downregulating Tryptase, COX2, and PGE2. Neonatal AA administration upregulated NGF and Sub-P; chronic SNS significantly decreased these pain biomarkers. Concurrently, chronic SNS increased ACh in colon tissues and vagal efferent activity. Conclusions: Sacral nerve stimulation reduces VH in rats and this ameliorating effect might be attributed to the suppression of mast cell overactivation in the colon tissue via the modulation of autonomic nervous system functions. Frontiers Media S.A. 2021-07-02 /pmc/articles/PMC8282909/ /pubmed/34276280 http://dx.doi.org/10.3389/fnins.2021.645393 Text en Copyright © 2021 Jin, Gharibani, Yin and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Jin, Xue
Gharibani, Payam
Yin, Jieyun
Chen, Jiande D. Z.
Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title_full Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title_fullStr Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title_full_unstemmed Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title_short Neuro-Immune Modulation Effects of Sacral Nerve Stimulation for Visceral Hypersensitivity in Rats
title_sort neuro-immune modulation effects of sacral nerve stimulation for visceral hypersensitivity in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282909/
https://www.ncbi.nlm.nih.gov/pubmed/34276280
http://dx.doi.org/10.3389/fnins.2021.645393
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