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

Abstract

Spinal cord stimulation (SCS) is increasingly used to treat painful diabetic neuropathy (PDN). At the time of a recent meta-analysis in this field, data were only available from randomized controlled trials (RCTs) of traditional low-frequency SCS (LF-SCS). However, outcomes from high-frequency 10 kHz SCS treatment are now available. Our study aimed to systematically review the contemporary evidence for SCS in patients with lower limb pain due to PDN and include an indirect comparison of the high- and low-frequency modalities. We searched the PubMed/CENTRAL databases up to 18 August 2022, for peer-reviewed RCTs of SCS that enrolled PDN patients with lower limb pain symptoms. The quality of the evidence was assessed with the Cochrane Risk of Bias tool. Using SCS treatment arm data from the RCTs, we indirectly compared the absolute treatment effect of 10 kHz SCS and LF-SCS. Results are presented in tables and forest plots. This systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Three RCTs met our eligibility criteria, including the recent 10 kHz SCS RCT (N = 216, 90 implanted) and 2 others that examined LF-SCS (N = 36, 17 implanted; N = 60, 37 implanted). Our analysis of 6-month data found clinically meaningful pain relief with each SCS modality. However, significantly greater pain reduction was identified for 10 kHz SCS over LF-SCS: average pain reduction in the 10 kHz SCS cohort was 73.7% compared with 47.5% in the pooled LF-SCS group (p < 0.0001). In the permanent implant subset, the 50% pain reduction responder rate was 83.3% in the 10 kHz SCS cohort versus 63.0% in the pooled LF-SCS group (p = 0.0072). The overall risk of bias of each included RCT was deemed high, mainly due to the absence of patient blinding. Our analysis indicates that paresthesia-free 10 kHz SCS can provide superior pain relief and responder rate over LF-SCS for managing PDN patients refractory to conventional medical management.

Clinical outcomes of spinal cord stimulation in patients with intractable leg pain in Japan

“…17 High-frequency SCS can provide superior pain relief and response rates over low-frequency SCS in patients with painful diabetic neuropathy refractory to conventional medical management. 18,19 The superiority of DTM SCS over traditional SCS for chronic low back pain, but not leg pain, has also been demonstrated. 7 However, in individual patients, modulation of nerve stimulation should be adjusted to maximize the effect of the therapy on microcirculation.…”

“…A device that provides ultrahigh‐frequency stimulation has also been manufactured 17 . High‐frequency SCS can provide superior pain relief and response rates over low‐frequency SCS in patients with painful diabetic neuropathy refractory to conventional medical management 18,19 . The superiority of DTM SCS over traditional SCS for chronic low back pain, but not leg pain, has also been demonstrated 7 .…”

The Invasive Management of Pain: Diagnosis and New Treatment Options

“…Instead, electrodes are placed anatomically based on pain site locations. Comparative studies of low-versus high-frequency spinal cord stimulation have been favorable in that high-frequency works as well if not better than low-frequency stimulation [67][68][69]. An intriguing and promising idea being studied now is the potentially synergistic combination of high-frequency spinal cord stimulation plus conventional low-frequency stimulation.…”

Variables associated with nonresponders to high‐frequency (10 kHz) spinal cord stimulation

“…6 Currently, SCS therapy is a valuable option in the treatment of painful diabetic neuropathy, persistent spinal pain syndrome (PSPS), nonsurgical low back and neck pain, lumbar radiculopathy refractory to conservative management, and complex regional pain syndrome (CRPS). [7][8][9][10][11][12][13][14] The expansion in therapeutic indications for SCS is derived from advancements in waveforms, programming, miniaturization of devices, sophistication of surgical technique, novel neural targets, and better comprehension of the mechanisms of action. These innovative and disruptive technological developments optimize electroceutical delivery to the spinal cord within the patient's therapeutic window for pain modulation with precision and efficacy, thereby contributing to better outcomes, safety, and cost-effectiveness.…”

“…It is estimated that approximately 50,000 SCS devices are implanted each year in the United States with an increasingly steady growth rate of 8%–10% annually 6 . Currently, SCS therapy is a valuable option in the treatment of painful diabetic neuropathy, persistent spinal pain syndrome (PSPS), nonsurgical low back and neck pain, lumbar radiculopathy refractory to conservative management, and complex regional pain syndrome (CRPS) 7–14 …”