Objectives: Diabetic distal symmetric polyneuropathy, affecting up to 50% of adults with diabetes, often leads to painful symptoms; yet current treatments are largely ineffective with standard therapies providing limited relief. The aim of this systematic review is to address the knowledge gap in understanding the neural networks associated with painful diabetic polyneuropathy (P-DPN). By synthesizing evidence from neuroimaging studies, it seeks to identify potential targets for neuromodulation-based treatments, ultimately guiding clinicians and researchers in developing novel, more effective therapeutic interventions for P-DPN.
Content: A comprehensive search following the preferred reporting items for systematic reviews and meta-analysis was conducted across Embase, PsycINFO, and MEDLINE databases to identify relevant neuroimaging studies from 2010 to May 2024. The search focused on studies involving P-DPN and excluded animal research. After the removal of duplicates and irrelevant studies, 18 studies were included and critically appraised for their contributions to understanding the neural correlates of P-DPN.
Summary: The review highlights that P-DPN is associated with alterations in brain networks involved in pain perception, particularly in the primary somatosensory cortex highlighting its role in sensory and pain perception. Regions such as the anterior cingulate cortex and thalamus exhibit altered functional connectivity, with the former showing responses to pain treatment. The review also identified increased connectivity between the cingulate cortex, medial prefrontal cortex, medial temporal region, and insula in individuals with P-DPN, pointing to the involvement of these regions in the emotional and cognitive aspects of pain processing.
Outlook: This review provides a foundational understanding of the neural networks involved in P-DPN, offering potential targets for future neuromodulation therapies. Further research is required to deepen the understanding of these brain alterations and to explore how they can be leveraged for more effective P-DPN treatments.
Keywords: brain imaging; neural networks; painful diabetic polyneuropathy; systematic review.
© 2025 the author(s), published by De Gruyter.