REVIEW article
Front. Mol. Neurosci.
Sec. Pain Mechanisms and Modulators
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1572775
Decoding Chronic Pain: The Glutamate-GABA Tug of War in the Cerebral Cortex
Provisionally accepted
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
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A sustained imbalance between excitatory and inhibitory mechanisms within the glutamatergic and GABAergic systems of the cerebral cortex, induced by noxious stimuli, is a fundamental characteristic in the development and maintenance of chronic pain. This review provides a comprehensive summary of the roles and interaction of glutamatergic and GABAergic systems in the processing of chronic pain signals. Specifically, we present a systematic summary of the processing patterns of the cerebral cortex in the cross-modular integration and output of chronic pain information, according to four aspects, molecular, cellular, neural network and behavioral cognition. These patterns consist of neuronal responses in individual cortical regions, neuron-astrocyte interactions, sharing and cascading of intercortical signals, and downward cortical modulation. Furthermore, a number of potential therapeutic approaches to the chronic pain are discussed from the pain management perspective.
Keywords: chronic pain1, cerebral cortex2, glutamatergic system3, GABAergic system4, Neural Network5
Received: 07 Feb 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Huang, Dong, He, Zhou, Zhou, Yang and Yu. 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:
Sha Yang, Chengdu University of Traditional Chinese Medicine, Chengdu, China
Shu-Guang Yu, Chengdu University of Traditional Chinese Medicine, Chengdu, 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.