PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress

Abstract Background Visceral pain sensitization and emotional reactions due to irritable bowel syndrome (IBS) occur frequently in the general population. Oxidative stress plays a crucial role in the pathogenesis of IBS. Previous studies have demonstrated that activation of peroxisome proliferator-ac...

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Main Authors: Minjie Li, Xiyu Zhuo, Yongxiao Liu, Jinchao You, Jianqing Lin
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Gastroenterology
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Online Access:https://doi.org/10.1186/s12876-025-03618-3
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author Minjie Li
Xiyu Zhuo
Yongxiao Liu
Jinchao You
Jianqing Lin
author_facet Minjie Li
Xiyu Zhuo
Yongxiao Liu
Jinchao You
Jianqing Lin
author_sort Minjie Li
collection DOAJ
description Abstract Background Visceral pain sensitization and emotional reactions due to irritable bowel syndrome (IBS) occur frequently in the general population. Oxidative stress plays a crucial role in the pathogenesis of IBS. Previous studies have demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) has analgesic effects. Therefore, we aimed to determine whether PPARγ activation ameliorates oxidative stress and affects thus nociceptive sensitization and emotional responses in IBS. Methods The study utilized male Sprague-Dawley (SD) rats, that suffered from neonatal colorectal distension (CRD), to assess the effects of various doses of rosiglitazone on visceral hyperalgesia and anxiety. Electromyography (EMG) of the external abdominal oblique muscles was used to evaluate visceral hypersensitivity, and Open Field Test (OFT) and Elevated Plus Maze (EPM) were used to evaluate anxiety. Superoxide dismutase (SOD) and malondialdehyde (MDA) in the spinal cord were analyzed by water-soluble tetrazolium-1 (WST-1) and thiobarbituric acid (TBA) methods, respectively, the expression levels of PPARγ in the spinal cord were assessed by qRT-PCR and Western blotting. Results Neonatal CRD-induced rats showed visceral pain sensitization and anxiety in adulthood, with down-regulated expression of PPARγ and SOD and elevated MDA levels in the spinal cord. Rosiglitazone alleviated visceral hypersensitivity and anxiety by activating PPARγ protein expression and promoting MDA up-regulation and SOD down-regulation in the spinal cord, which were reversed by GW9662, an antagonist of PPARγ. Conclusion This study demonstrated that rosiglitazone alleviated visceral pain sensitization and anxiety in male IBS rats by alleviating oxidative stress through activation of PPARγ.
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spelling doaj-art-48cc27cb12bf45079f2a170291b14f7f2025-01-26T12:36:18ZengBMCBMC Gastroenterology1471-230X2025-01-0125111310.1186/s12876-025-03618-3PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stressMinjie Li0Xiyu Zhuo1Yongxiao Liu2Jinchao You3Jianqing Lin4Department of Anesthesiology, First Affiliated Hospital, Fujian Medical UniversityDepartment of Anesthesiology, Fujian Provincial HospitalDepartment of Anesthesiology, First Affiliated Hospital, Fujian Medical UniversityDepartment of Anesthesiology, First Affiliated Hospital, Fujian Medical UniversityDepartment of Anesthesiology, First Affiliated Hospital, Fujian Medical UniversityAbstract Background Visceral pain sensitization and emotional reactions due to irritable bowel syndrome (IBS) occur frequently in the general population. Oxidative stress plays a crucial role in the pathogenesis of IBS. Previous studies have demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) has analgesic effects. Therefore, we aimed to determine whether PPARγ activation ameliorates oxidative stress and affects thus nociceptive sensitization and emotional responses in IBS. Methods The study utilized male Sprague-Dawley (SD) rats, that suffered from neonatal colorectal distension (CRD), to assess the effects of various doses of rosiglitazone on visceral hyperalgesia and anxiety. Electromyography (EMG) of the external abdominal oblique muscles was used to evaluate visceral hypersensitivity, and Open Field Test (OFT) and Elevated Plus Maze (EPM) were used to evaluate anxiety. Superoxide dismutase (SOD) and malondialdehyde (MDA) in the spinal cord were analyzed by water-soluble tetrazolium-1 (WST-1) and thiobarbituric acid (TBA) methods, respectively, the expression levels of PPARγ in the spinal cord were assessed by qRT-PCR and Western blotting. Results Neonatal CRD-induced rats showed visceral pain sensitization and anxiety in adulthood, with down-regulated expression of PPARγ and SOD and elevated MDA levels in the spinal cord. Rosiglitazone alleviated visceral hypersensitivity and anxiety by activating PPARγ protein expression and promoting MDA up-regulation and SOD down-regulation in the spinal cord, which were reversed by GW9662, an antagonist of PPARγ. Conclusion This study demonstrated that rosiglitazone alleviated visceral pain sensitization and anxiety in male IBS rats by alleviating oxidative stress through activation of PPARγ.https://doi.org/10.1186/s12876-025-03618-3Irritable bowel syndromeVisceral pain sensitivityAnxietyPPARγOxidative stress
spellingShingle Minjie Li
Xiyu Zhuo
Yongxiao Liu
Jinchao You
Jianqing Lin
PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
BMC Gastroenterology
Irritable bowel syndrome
Visceral pain sensitivity
Anxiety
PPARγ
Oxidative stress
title PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
title_full PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
title_fullStr PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
title_full_unstemmed PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
title_short PPARγ activation attenuates neonatal CRD-induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
title_sort pparγ activation attenuates neonatal crd induced visceral pain sensitization and anxiety in male rats by alleviating oxidative stress
topic Irritable bowel syndrome
Visceral pain sensitivity
Anxiety
PPARγ
Oxidative stress
url https://doi.org/10.1186/s12876-025-03618-3
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