Decoding chronic pain: the glutamate-GABA tug of war in the cerebral cortex

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 th...

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Bibliographic Details
Main Authors: Dan Huang, Yu-Ting Dong, Liu-Xuan He, Rui-Zhu Zhou, Jian-Xiong Zhou, Sha Yang, Shu-Guang Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2025.1572775/full
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Summary: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 inter-cortical signals, and downward cortical modulation. Furthermore, a number of potential therapeutic approaches to the chronic pain are discussed from the pain management perspective.
ISSN:1662-5099