Diabetic Neuropathy and Spinal Cord Stimulation: A Brief Background

Diabetes is the fourth most common disease worldwide, affecting 5.9% of the world’s population.1 A common complication of the disease is diabetic neuropathy, affecting nearly 30% of individuals with diabetes. Categorized by chronic sensory loss that progresses proximally from the feet and hands in a stocking-and-glove pattern, diabetic neuropathy can unfortunately develop further into painful diabetic neuropathy (PDN) with burning pain and paresthesia.2 PDN can accordingly negatively affect quality of life, resulting in depression, anxiety, and decreased sleep.3

Low Frequency SCS

Historically, when these agents failed or caused intolerable side effects, some clinicians would turn to low-frequency spinal cord stimulation (LF-SCS). LF-SCS, a common treatment for neuropathic pain, emits electrical pulses to the spinal cord at 40 Hz to 60 Hz resulting in therapeutic paresthesia in the covered dermatomes. These paresthesias were often not tolerated by patients with PDN, and LF-SCS has been shown to lose effectiveness over time.5–7

High Frequency SCS

Over the past decade, higher frequency SCS (HF-SCS) at 10 kHz has been introduced and utilized for various chronic pain syndromes. HF-SCS has been demonstrated to be effective in treating other types of neuropathic pain, and, unlike LF-SCS, does not induce paresthesia.8–11 Its primary proposed mechanism of action is by selectively activating inhibitory interneurons in the dorsal horn, suppressing the hyperexcitable wide dynamic range neurons that are typically overactive in chronic pain conditions.12,13 The approach reportedly uses a low stimulation intensity, thereby not activating the dorsal column fibers. Other theorized mechanisms of action include acting on the medial pathway (responsible for attention and pain perception) as well as lateral pathways, desynchronization of neural signals, reversible blockade of depolarization, glial-neuronal interaction, membrane integration, and induced temporal summation.12

Test your clinical knowledge of SCS and its application in managing diabetic neuropathy with these 3 questions. Hit submit to see the answers.

1. SCS emitting electrical pulses to the spinal cord at ___ commonly results in therapeutic paresthesia in the painful dermatomes
2. Which of the following has been shown to be most effective in treating painful diabetic neuropathy resistant to medical management?
3. True/False: High-frequency SCS does not induce therapeutic paresthesia in the painful dermatomes and has been shown to increase sensory neurological improvement.
Evidence for SCS to Treat Painful Diabetic Neuropathy

RCTs within the past decade assessing SCS for the treatment of PDN include those by Slangen et al (2014),5 de Vos et al (2014),14 and Petersen et al (2021).15 Slangen et al and de Vos et al compared LF-SCS to medical management, while Petersen et al compared HF-SCS to medical management.

Following these trials, Hoelzer et al pooled the data to indirectly compare LF-SCS to HF-SCS.14 Data from Hoelzer et al showed both forms of SCS to be superior to medical management for pain reduction for patients with PDN, with a mean reduction in pain intensity from baseline over 30% – greater than the calculated minimum clinically important difference (MCID). Additionally, subjects treated with HF-SCS reported a 5.6-point decrease in mean pain score from baseline (2.8 times the MCID), while the LF-SCS group had a 3.4-point decrease (1.7 times the MCID). While both were clinically and statistically significant compared to medical management, the HF-SCS group’s pain reduction was also clinically and statistically significantly superior to the LF-SCS group. Moreover, the HF-SCS group was more likely to experience a reduction in pain from baseline 6 months after SCS implantation when compared to the LF-SCS group.14

Adverse Events from HF-SCS

Adverse events in the 6 months of follow-up for the RCTs included postimplant infection (ranging from 0% to 5.9% depending on the trial), implantable pulse generator (IPG) site pain (1.1% to 5.4%), and uncomfortable stimulation (1.1%).15 Of the 208 total implants (including the 64 crossover implants for Petersen et al’s 12-month follow up), there was a 1.0% instance of lead migration, 1.9% of lead revisions (2 due to lead migration, 2 due to incomplete paresthesia overlap), 1.9% of IPG revisions (2 of 4 due to IPG site pain), 2.9% explants due to infection, and zero IPG replacements.11 There was also a 1.9% incidence of wound dehiscence, and 0.9% incidence of impaired healing, device extrusion, incision site pain, dural puncture with subdural hematoma sequela, and coagulopathy during implantation.14

Practical Takeaways

As SCS’ clinical applicability continues to expand, pain physicians should be aware of the utility of different stimulation frequencies. Higher frequency 10 kHz HF-SCS appears to be more effective than traditional 40 Hz to 60 Hz LF-SCS for reducing pain in PDN refractory to medical management, echoing findings in previous studies analyzing it for chronic back and leg pain.16,17 Data support its use over LF-SCS at the 6-month and 12-month follow-up intervals in the studies above, and unlike LF-SCS, it has the added benefit of not inducing paresthesia in patients with PDN who may already experience it at baseline. In fact, Petersen et al found that 62% of patients experienced neurological improvement assessed on physical exam following 6 months of 10-kHz SCS, a finding replicated in other studies as well.18,19

However, it is important to weigh these potential advantages with adverse events, in particular postimplant infection given that it was the most common complication (up to 5.9% depending on the trial, with 2.9% of total implants necessitating explant due to infection). It is important to note that patients with PDN may be more susceptible to infection given their underlying diabetes. The primary 3 RCTs referenced in this article also had notably high risks of bias given that they were unblinded studies with patient-reported outcomes. Although common with SCS trials, subjects nonetheless knew whether they had an SCS implanted or only received medical management.

Consequently, while pain physicians should strongly consider utilizing 10 kHz-SCS for treating PDN refractory to medical management, it is important to keep these studies’ shortcomings in mind and continue to watch for further higher-quality greater-powered studies to emerge.

  1. Chan JCN, LiReferencesm L-L, Wareham NJ, et al. The Lancet Commission on diabetes: using data to transform diabetes care and patient lives. Lancet (London, England). 2021;396(10267):2019-2082. doi:10.1016/S0140-6736(20)32374-6
  2. Baxi H, Habib A, Hussain MS, Hussain S, Dubey K. Prevalence of peripheral neuropathy and associated pain in patients with diabetes mellitus: Evidence from a cross-sectional study. J Diabetes Metab Disord. 2020;19(2):1011-1017. doi:10.1007/s40200-020-00597-y
  3. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000;47(2):123-128. doi:10.1016/s0168-8227(99)00112-6
  4. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-154. doi:10.2337/dc16-2042
  5. 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. doi:10.2337/dc14-0684
  6. van Beek M, Slangen R, Schaper NC, et al. Sustained Treatment Effect of Spinal Cord Stimulation in Painful Diabetic Peripheral Neuropathy: 24-Month Follow-up of a Prospective Two-Center Randomized Controlled Trial. Diabetes Care. 2015;38(9):e132-4. doi:10.2337/dc15-0740
  7. van Beek M, Geurts JW, Slangen R, et al. Severity of Neuropathy Is Associated With Long-term Spinal Cord Stimulation Outcome in Painful Diabetic Peripheral Neuropathy: Five-Year Follow-up of a Prospective Two-Center Clinical Trial. Diabetes Care. 2018;41(1):32-38. doi:10.2337/dc17-0983
  8. Gupta M, Scowcroft J, Kloster D, et al. 10-kHz Spinal Cord Stimulation for Chronic Postsurgical Pain: Results From a 12-Month Prospective, Multicenter Study. Pain Pract. 2020;20(8):908-918. doi:10.1111/papr.12929
  9. Tate JL, Stauss T, Li S, Rotte A, Subbaroyan J. A Prospective, Multi-Center, Clinical Trial of a 10-kHz Spinal Cord Stimulation System in the Treatment of Chronic Pelvic Pain. Pain Pract. 2021;21(1):45-53. doi:10.1111/papr.12932
  10. Amirdelfan K, Vallejo R, Benyamin R, et al. High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Combined Neck and Arm Pain: Results From a Prospective Multicenter Study. Neurosurgery. 2020;87(2):176-185. doi:10.1093/neuros/nyz495
  11. Kapural L, Jameson J, Johnson C, et al. Treatment of nonsurgical refractory back pain with high-frequency spinal cord stimulation at 10 kHz: 12-month results of a pragmatic, multicenter, randomized controlled trial. J Neurosurg Spine. February 2022:1-12. doi:10.3171/2021.12.SPINE211301
  12. Tieppo Francio V, Polston KF, Murphy MT, Hagedorn JM, Sayed D. Management of Chronic and Neuropathic Pain with 10 kHz Spinal Cord Stimulation Technology: Summary of Findings from Preclinical and Clinical Studies. Biomedicines. 2021;9(6). doi:10.3390/biomedicines9060644
  13. Lee KY, Bae C, Lee D, et al. Low-intensity, Kilohertz Frequency Spinal Cord Stimulation Differently Affects Excitatory and Inhibitory Neurons in the Rodent Superficial Dorsal Horn. Neuroscience. 2020;428:132-139. doi:10.1016/j.neuroscience.2019.12.031
  14. Hoelzer BC, Edgar D, Lu S-P, Taylor RS. Indirect Comparison of 10 kHz Spinal Cord Stimulation (SCS) versus Traditional Low-Frequency SCS for the Treatment of Painful Diabetic Neuropathy: A Systematic Review of Randomized Controlled Trials. Biomedicines. 2022;10(10). doi:10.3390/biomedicines10102630
  15. Petersen EA, Stauss TG, Scowcroft JA, et al. Durability of High-Frequency 10-kHz Spinal Cord Stimulation for Patients With Painful Diabetic Neuropathy Refractory to Conventional Treatments: 12-Month Results From a Randomized Controlled Trial. Diabetes Care. 2022;45(1):e3-e6. doi:10.2337/dc21-1813
  16. Kapural L, Yu C, Doust MW, et al. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. 2015;123(4):851-860. doi:10.1097/ALN.0000000000000774
  17. Kapural L, Yu C, Doust MW, et al. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial. Neurosurgery. 2016;79(5):667-677. doi:10.1227/NEU.0000000000001418
  18. 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. JAMA Neurol. 2021;78(6):687-698. doi:10.1001/jamaneurol.2021.0538
  19. Schnapp WD, Delcroix GJ-R. Improved Sensation Resulting From Spinal Cord Stimulation for the Treatment of Painful Diabetic Neuropathy: The Possible Role of Stochastic Resonance. Pain Physician. 2022;25(9):E1399-E1403.