Painful diabetic peripheral neuropathy (PDN) affects roughly one in five people living with diabetes and is among the most difficult complications to treat. Burning, shooting, or electric-shock pain in the feet and legs disrupts sleep, mobility, and quality of life, yet first-line oral medications such as duloxetine, pregabalin, gabapentin, and tricyclic antidepressants provide meaningful relief for only a minority of patients and often carry sedation, dizziness, and other dose-limiting side effects. For patients whose pain persists despite optimized medical management, spinal cord stimulation (SCS) has emerged as an evidence-supported option. This article reviews how the therapy works and what recent randomized trials demonstrate.
What Spinal Cord Stimulation Is
Spinal cord stimulation delivers low-energy electrical pulses to the dorsal epidural space through thin leads placed near the spinal cord. A small pulse generator, implanted under the skin after a successful trial period, powers the system. By modulating the transmission of pain signals before they reach the brain, SCS aims to reduce the perception of neuropathic pain without the systemic exposure of oral drugs. Traditional, low-frequency “tonic” stimulation produces a tingling sensation called paresthesia in the painful area, whereas newer high-frequency 10-kHz stimulation provides relief without that sensation.
Early Randomized Evidence with Low-Frequency Stimulation
The foundational randomized data came from low-frequency tonic SCS. In a prospective two-center randomized controlled trial published in Diabetes Care in 2014, Slangen and colleagues compared SCS plus best medical therapy against best medical therapy alone in patients with refractory PDN of the lower limbs. Treatment success—defined as at least 50% pain relief or a meaningful improvement on a patient global impression scale—was achieved far more often in the stimulation group, establishing proof of concept that neuromodulation could relieve pain that drugs could not. These early studies, however, involved relatively small numbers and used the paresthesia-based approach.
High-Frequency 10-kHz Stimulation: The SENZA-PDN Trial
The most robust evidence to date comes from the SENZA-PDN study, the largest randomized controlled trial of SCS for this condition. Reported by Petersen and colleagues in JAMA Neurology in 2021, the trial randomized 216 patients with refractory PDN to either 10-kHz SCS combined with conventional medical management or conventional medical management alone, with the option to cross over after six months. At six months, 79% of patients in the stimulation group achieved the primary endpoint of at least 50% pain relief without worsening of neurological function, compared with only a small fraction of those receiving medication alone. Average pain relief in the stimulation group approached 76%.
Durability at 24 Months
A key question for any chronic-pain therapy is whether benefit lasts. The 24-month results, published in Diabetes Research and Clinical Practice in 2023, followed 142 patients implanted with a 10-kHz system, including those who crossed over from medical management. At two years, mean pain had fallen by 79.9% from baseline, and 90.1% of participants reported at least 50% pain relief. Participants also reported significant improvements in sleep and health-related quality of life. Notably, 65.7% demonstrated a clinically meaningful improvement on neurological examination—a finding that suggests the therapy may do more than mask symptoms, though the mechanism and clinical significance of this observation remain under investigation.
Safety and Patient Selection
SCS is an invasive therapy and is generally reserved for patients with lower-limb PDN that remains disabling despite an adequate trial of guideline-based pharmacotherapy. Because the leads and generator are implanted, the principal risks are procedure related, most importantly infection. In the SENZA-PDN cohort, roughly 3% of implanted systems required removal because of infection. A trial stimulation period before permanent implantation allows clinicians and patients to confirm that an individual responds before committing to the device. A 2021 systematic review in Pain and Therapy synthesizing the available randomized and observational data concluded that SCS offers durable pain relief for carefully selected patients with refractory PDN, while emphasizing the importance of appropriate candidate selection and infection-prevention measures.
Clinical Takeaways
For people with painful diabetic neuropathy that does not respond to optimized oral therapy, spinal cord stimulation—particularly high-frequency 10-kHz stimulation—is now supported by randomized evidence showing substantial and durable pain relief, with benefits sustained to at least two years and accompanied by improvements in sleep and quality of life. The therapy is not a first-line treatment and is not a substitute for glycemic control, foot protection, and the broader management of diabetes, which remain essential to limit progression of neuropathy. The principal risks are surgical, and careful patient selection through a trial stimulation period helps identify those most likely to benefit. As longer-term registry data accumulate, neuromodulation is increasingly recognized as a meaningful option within the wider strategy for managing refractory diabetic neuropathic pain.
References
Slangen R, Schaper NC, Faber CG, et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial. Diabetes Care. 2014;37(11):3016–3024.
Petersen EA, Stauss TG, Scowcroft JA, et al. Effect of high-frequency (10-kHz) spinal cord stimulation in patients with painful diabetic neuropathy: a randomized clinical trial (SENZA-PDN). JAMA Neurology. 2021;78(6):687–698.
Petersen EA, Stauss TG, Scowcroft JA, et al. Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-month results of a randomized controlled trial. Diabetes Research and Clinical Practice. 2023;203:110865.
Spinal cord stimulation for painful diabetic peripheral neuropathy: a systematic review. Pain and Therapy. 2021;10(2):1303–1320.
Spinal cord stimulation in painful diabetic neuropathy: an overview. Diabetes Research and Clinical Practice. 2024;208:111104.
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