AUTHOR=Huang Dan , Dong Yu-Ting , He Liu-Xuan , Zhou Rui-Zhu , Zhou Jian-Xiong , Yang Sha , Yu Shu-Guang 

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

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 18 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2025.1572775

DOI=10.3389/fnmol.2025.1572775

ISSN=1662-5099

ABSTRACT=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.