Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications

Emerging evidence has illuminated the pivotal role of gut microbiota in modulating pain sensitivity through bidirectional gut-brain interactions. Current research demonstrates that gut microbial communities significantly influence pain perception by regulating both central and peripheral sensitizati...

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Main Authors: Minghe Zhao, Ling Zhang, Zhihui Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pain Research
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpain.2025.1626515/full
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author Minghe Zhao
Minghe Zhao
Ling Zhang
Zhihui Liu
author_facet Minghe Zhao
Minghe Zhao
Ling Zhang
Zhihui Liu
author_sort Minghe Zhao
collection DOAJ
description Emerging evidence has illuminated the pivotal role of gut microbiota in modulating pain sensitivity through bidirectional gut-brain interactions. Current research demonstrates that gut microbial communities significantly influence pain perception by regulating both central and peripheral sensitization mechanisms across various pain modalities. This review synthesizes current knowledge on the mechanisms underlying gut microbiota-mediated pain sensitization, encompassing: (1) cross-talk within the microbiome-gut-brain axis, (2) regulatory effects of microbial metabolites on central and peripheral sensitization pathways, and (3) bioactive compounds derived from gut microbiota that participate in pain modulation. Furthermore, we systematically evaluate the therapeutic potential of microbiota-targeted interventions including probiotic supplementation, fecal microbiota transplantation, and dietary modifications in pain management. To advance this promising field, future investigations should prioritize three key directions: establishing causal relationships through rigorous verification, accelerating clinical translation of preclinical findings, and developing personalized microbial-based therapeutic strategies.
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publisher Frontiers Media S.A.
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series Frontiers in Pain Research
spelling doaj-art-e4d2db950ead4965ac243b366276cb852025-08-20T03:28:50ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2025-07-01610.3389/fpain.2025.16265151626515Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implicationsMinghe Zhao0Minghe Zhao1Ling Zhang2Zhihui Liu3Department of Anesthesiology, Baotou Central Hospital, Baotou, ChinaBaotou Clinical Medical College, Inner Mongolia Medical University, Baotou, ChinaDepartment of Gastroenterology, Baotou Central Hospital, Baotou, ChinaDepartment of Anesthesiology, Baotou Central Hospital, Baotou, ChinaEmerging evidence has illuminated the pivotal role of gut microbiota in modulating pain sensitivity through bidirectional gut-brain interactions. Current research demonstrates that gut microbial communities significantly influence pain perception by regulating both central and peripheral sensitization mechanisms across various pain modalities. This review synthesizes current knowledge on the mechanisms underlying gut microbiota-mediated pain sensitization, encompassing: (1) cross-talk within the microbiome-gut-brain axis, (2) regulatory effects of microbial metabolites on central and peripheral sensitization pathways, and (3) bioactive compounds derived from gut microbiota that participate in pain modulation. Furthermore, we systematically evaluate the therapeutic potential of microbiota-targeted interventions including probiotic supplementation, fecal microbiota transplantation, and dietary modifications in pain management. To advance this promising field, future investigations should prioritize three key directions: establishing causal relationships through rigorous verification, accelerating clinical translation of preclinical findings, and developing personalized microbial-based therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fpain.2025.1626515/fullpaingut microbiotamicrobiome-gut-brain axissensitizationneuroinflammationGPR43
spellingShingle Minghe Zhao
Minghe Zhao
Ling Zhang
Zhihui Liu
Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
Frontiers in Pain Research
pain
gut microbiota
microbiome-gut-brain axis
sensitization
neuroinflammation
GPR43
title Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
title_full Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
title_fullStr Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
title_full_unstemmed Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
title_short Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications
title_sort gut microbiota mediated pain sensitization mechanisms and therapeutic implications
topic pain
gut microbiota
microbiome-gut-brain axis
sensitization
neuroinflammation
GPR43
url https://www.frontiersin.org/articles/10.3389/fpain.2025.1626515/full
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AT zhihuiliu gutmicrobiotamediatedpainsensitizationmechanismsandtherapeuticimplications