REVIEW article
Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1637357
The Role of Brain Mechanisms in Diabetic Peripheral Neuropathy: Recent Advances and Comprehensive Analysis
Provisionally accepted
- 1Department of Anesthesiology, Peking University Third Hospital, Beijing, China
- 2Peking University Neuroscience Research Institute, Beijing, China
- 3Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- 4Key Laboratory for Neuroscience, National Health Commission of the People's Republic of China, Beijing, China
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Diabetic peripheral neuropathy (DPN), a prevalent and debilitating complication of diabetes, involves complex interactions between peripheral nerve damage and central nervous system (CNS) dysfunction. While traditional research has focused on peripheral and spinal mechanisms, emerging evidence highlights that the brain plays a critical role in the development of painful DPN. This review synthesizes recent advances from neuroimaging, spectroscopy, and preclinical studies to delineate structural, functional, and neurochemical alterations in the central nervous system associated with DPN. Patients exhibit cortical thinning, subcortical atrophy, and disrupted connectivity in sensory, affective, and cognitive networks, accompanied by metabolic imbalances and excitatory–inhibitory neurotransmitter shifts. Preclinical models further implicate maladaptive plasticity, microglial activation, and region-specific astrocytic responses in amplifying central sensitization and pain chronicity. These mechanistic insights underscore the central nervous system as a therapeutic target. Non-invasive neuromodulation techniques, such as repetitive transcranial magnetic stimulation, and brain-directed pharmacological strategies show promising but preliminary benefits in alleviating neuropathic pain. Understanding the interplay between peripheral injury and brain dysfunction in DPN not only broadens the conceptual framework of its pathophysiology but also provides a foundation for developing novel interventions aimed at restoring central network balance and improving patient outcomes.
Keywords: Diabetic peripheral neuropathy, Brain mechanisms, Neuroimaging, Neuroinflammation, Neuromodulation
Received: 29 May 2025; Accepted: 08 Oct 2025.
Copyright: © 2025 Wei, Jiang, Shou, Xing and Li. 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:
Guo-Gang Xing, ggxing@bjmu.edu.cn
Min Li, liminanesth@bjmu.edu.cn
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.