Structural and Functional Impact of Spinal Cord Stimulation in Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes that leads to chronic pain, sensory loss, and functional decline. While spinal cord stimulation (SCS) is FDA-approved for painful diabetic neuropathy, its potential to modify disease pathology rather than merely suppress symptoms remains poorly understood. This narrative review bridges this knowledge gap by elucidating the role of SCS in mitigating structural and functional changes in the spinal cord and the peripheral nervous system in DPN. A systematic PubMed search for studies published between January 1990 and May 2025 on the structural, functional, vascular, or biochemical effects of SCS in diabetic neuropathy yielded 361 records, of which 22 met the inclusion criteria. Data were extracted thematically across five domains: peripheral nerve structure, spinal plasticity, supraspinal modulation, neuroinflammation, and vascular/metabolic effects. SCS consistently improved both functional and structural biomarkers of neuropathy. In clinical studies, SCS enhanced nerve conduction velocity, increased intraepidermal nerve fiber density, and promoted corneal nerve regeneration within 6-12 months. Preclinical data demonstrated suppression of microglial activation, downregulation of pro-inflammatory mediators, and restoration of neurotrophic signaling. SCS also improved spinal and peripheral microcirculation and reversed metabolic and vascular dysregulation associated with hyperglycemia. Collectively, these effects suggest that SCS has multimodal benefits that can restore neural integrity, recalibrate neuroimmune pathways, and mitigate disease progression in DPN. These findings position SCS as a potential disease-modifying therapy for DPN and underscore the need for prospective mechanistic trials integrating structural and functional biomarkers to refine patient selection and optimize neuromodulation outcomes.