REVIEW article
Front. Pain Res.
Sec. Pain Mechanisms
Volume 6 - 2025 | doi: 10.3389/fpain.2025.1626515
Gut Microbiota-Mediated Pain Sensitization: Mechanisms and Therapeutic Implications
Provisionally accepted
- 1Department of Anesthesiology, Baotou Central Hospital, Baotou, China
- 2Baotou Clinical Medical College, Inner Mongolia Medical University, Baotou, China
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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.
Keywords: Pain, Gut Microbiota, microbiome-gut-brain axis, sensitization, Neuroinflammation, GPR43, TLR2
Received: 11 May 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Zhao and Liu. 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) or licensor 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.
* Correspondence:
Minghe Zhao, Department of Anesthesiology, Baotou Central Hospital, Baotou, China
Zhihui Liu, Department of Anesthesiology, Baotou Central Hospital, Baotou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.