Cerebral alterations associated with painful diabetic peripheral neuropathy

Abstract Painful diabetic peripheral neuropathy (PDN) is a serious and debilitating complication of diabetes, characterized by persistent neuropathic pain that significantly compromises patients’ quality of life. While the pathogenesis of PDN has historically been investigated primarily through peripheral nerve and spinal cord pathology, recent evidence increasingly underscores the contribution of cerebral changes to the onset and persistence of this condition. This review synthesizes current knowledge regarding structural and functional alterations in key brain regions associated with PDN, including the thalamus, striatum, anterior cingulate cortex, insular cortex, and hippocampus. Additionally, it explores the role of the descending pain modulatory system and other cerebral structures in the pathophysiology of PDN. Further research is warranted to elucidate the mechanisms driving these cerebral changes and to evaluate their potential as therapeutic targets for improving PDN management.