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
Dan  HuangDan HuangYu-Ting  DongYu-Ting DongLiu-Xuan  HeLiu-Xuan HeRui-Zhu  ZhouRui-Zhu ZhouJian-Xiong  ZhouJian-Xiong ZhouSha  YangSha Yang*Shu-Guang  YuShu-Guang Yu*
  • Chengdu University of Traditional Chinese Medicine, Chengdu, China

The final, formatted version of the article will be published soon.

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

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