Low-frequency Spinal Cord Stimulation Research Articles

Motor improvement and spasms recovery with high-frequency 10kHz spinal cord stimulation in a patient with spastic tetraparesis: beyond pain relief.

To describe the clinical outcomes beyond pain relief of high-frequency spinal cord stimulation at 10kHz (10kHz SCS) in a patient with cervical myelopathy and drug-resistant chronic neuropathic pain with spastic tetraparesis. A patient with C3-C6 myelomalacia and spastic tetraparesis previously treated with decompressive laminectomy underwent implantation of 10kHz SCS for pain management through a trial procedure followed by permanent implantation. Due to the presence of epidural fibrotic scar tissue in the area of the previous C3-C6 laminectomy, the leads could not be implanted at the cervical level; therefore, the leads were positioned at the thoracic level. Data were collected during routine follow-up visits up to 15 months after implantation. Since the trialing phase and during all follow-up visits, along with complete pain relief in the lower limbs, a recovery from spasms was observed with an improvement in motor function. The patient recovered from a sensation of stiffness and difficulty in movement, with a significant decrease in muscle tone, regaining confidence in walking, and no longer needing assistance even for long walking distances. Although all disabling and painful symptomatology in the upper limbs instead did not ameliorate, the Oswestry Disability Index (ODI) score decreased from 50% at baseline to 6%. To our knowledge, recovery from spasms and motor improvement in a spastic tetraparesis patient has never been reported before with 10kHz SCS and possibly this new stimulation paradigm may overcome some performance limitations of traditional low-frequency SCS (LF-SCS). Treatment eliminated spasms at the lower limbs but not at the upper ones, thus suggesting that the location of the epidural leads could affect outcomes.

Is it possible to generate an additional pleasant and pain-relieving muscle stimulation when using a low-frequency spinal cord stimulation (SCS) for the treatment of lower back pain? Pilot study: A new technique: "MuscleSCS".

The combined use of spinal cord stimulation (SCS) and muscle stimulation, in the treatment of chronic pain, using the same probe, could improve the clinical results. However, this technique has not been established as yet. It was our hypothesis that it is possible to generate muscle stimulation by using low frequencies with SCS electrodes and use it to additionally treat chronic back pain. We generated muscle stimulation in patients with previously implanted SCS electrodes, for the treatment of lower back pain, by using low frequencies (2, 4, 6, and 8 Hz) and different contact combinations of the electrodes. The results were evaluated by using visual inspection (videos), haptic control, surface electromyography (EMG), and sonographic recordings. This pilot study (17 patients, seven females, age 36-87 years, 11 percutaneous paddle leads, and 6 octrodes) was performed at the Neurosurgical Department of the University of Tuebingen. The most preferred frequencies were 6 Hz (45.5% of percutaneous paddle leads) and 8 Hz (50% of octrodes) at contacts 3&4 or 5&6. The preference of frequencies differed significantly among genders (p = 0.023). Simultaneous EMG and ultrasonic recordings demonstrated the generation of muscle potentials and the stimulation of deeper muscle groups. In this study, it has been shown that with low-frequency SCS stimulation, pleasant and pain-relieving muscle contractions of the lower and upper back can also be generated. This combined method has been coined by us as "MuscleSCS" technique. Clinical trials are necessary to establish the value of this combined technique and its subtypes.

Novel Pulsed-Ultrahigh-Frequency Spinal Cord Stimulation Inhibits Mechanical Hypersensitivity and Brain Neuronal Activity in Rats after Nerve Injury.

Spinal cord stimulation (SCS) is an important pain treatment modality. We hypothesized that a novel pulsed-ultrahigh-frequency SCS (pUHF-SCS) could safely and effectively inhibit spared nerve injury-induced neuropathic pain in rats. Epidural pUHF-SCS (± 3V, 2Hz pulses comprising 500 kHz biphasic sinewaves) was implanted at the thoracic vertebrae (T9-T11). Local field brain potentials following hind paw stimulation were recorded. Analgesia was evaluated by von-Frey-evoked allodynia and acetone-induced cold allodynia. The mechanical withdrawal threshold of the injured paw was 0.91 ± 0.28 g lower than that of the sham surgery (24.9 ± 1.2 g). Applying 5-, 10-, or 20-minute pUHF-SCS five times every two days significantly increased the paw withdrawal threshold to 13.3 ± 6.5, 18.5 ± 3.6, and 21.0 ± 2.8 g at 5 hours post-SCS, respectively (p = 0.0002, < 0.0001, and < 0.0001; n = 6/group), and to 6.1 ± 2.5, 8.2 ± 2.7, and 14.3 ± 5.9 g on the second day, respectively (p = 0.123, 0.013, and < 0.0001). Acetone-induced paw response numbers decreased from pre-SCS (41 ± 12) to 24 ± 12 and 28 ± 10 (p = 0.006 and 0.027; n = 9) at 1 and 5 hours post-three rounds of 20-minute pUHF-SCS, respectively. The areas under the curve from the C component of the evoked potentials at the left primary somatosensory and anterior cingulate cortices were significantly decreased from pre-SCS (101.3 ± 58.3 and 86.9 ± 25.5, respectively) to 39.7 ± 40.3 and 36.3 ± 20.7 (p = 0.021, and 0.003; n = 5) at 60 minutes post-SCS, respectively. The intensity thresholds for pUHF-SCS to induce brain and sciatic nerve activations were much higher than the therapeutic intensities and thresholds of conventional low-frequency SCS. pUHF-SCS inhibited neuropathic pain-related behavior and paw stimulation evoked brain activation through mechanisms distinct from low-frequency SCS.

ID: 220244 A Single-Center Review of 10 kHz Spinal Cord Stimulator Treatment Outcomes for Chronic Pain

Chronic pain is a prevalent worldwide condition, leading to diminished quality of life and workforce productivity (1). First-line therapies from conservative medical management to surgery have demonstrated varying degrees of efficacy, though sustained long-term pain management remains a challenge (2). Low-frequency spinal cord stimulation (LF-SCS) has been used in a subset of patients as a cost-effective and minimally invasive therapy to achieve pain control and improved quality of life (3). However, its limitations include diminished long-term relief, uncomfortable paresthesia, and incomplete pain control (4). The pivotal SENZA-RCT in 2015 demonstrated the efficacy of 10 kHz (high-frequency) spinal cord stimulation (HF-SCS) as a superior alternative to LF-SCS (5). The study, although promising, was industry-sponsored and potentially vulnerable to bias including withholding of negative data or exaggeration of beneficial effects. The goal of this single-center retrospective review was to compare outcomes of real-world/pragmatic HF-SCS pain outcomes to previously published studies without the potential bias of industry funding.

ID: 216095 High-Frequency Spinal Cord Stimulation (SCS) in Patients Converted From Traditional SCS: A Case Series

Spinal cord stimulation (SCS) is an evidence-based intervention for treating chronic neuropathic pain1. However, with traditional SCS, around 30% of patients may require explant for reasons including loss of efficacy during treatment2. High-frequency SCS (10kHz SCS) has been reported to demonstrate long-term superiority compared to traditional low-frequency (LF) SCS3. Furthermore, converting from LF to 10kHz SCS can restore pain relief in patients experiencing loss of efficacy4. In this study, we present a case series of 6 patients converted from LF SCS to 10kHz therapy due to loss of efficacy.

Low- and high-frequency spinal cord stimulation and arterial blood pressure in patients with chronic pain and hypertension: a retrospective study.

Evidence suggests that traditional low-frequency spinal cord stimulation (LF-SCS) reduces arterial blood pressure (BP) in patients with chronic pain and hypertension independent of improved pain symptoms. However, it remains unclear whether high-frequency spinal cord stimulation (HF-SCS) also lowers BP in chronic pain patients with hypertension. Therefore, in a retrospective study design, we tested the hypothesis that clinic BP would be significantly reduced following implantation of HF-SCS in patients with chronic pain and hypertension. Clinic BP within 3months before and after surgical implantation of either a LF-SCS or HF-SCS device between 2010 and 2020 were collected from electronic medical records at The University of Kansas Health System (TUKHS). A total of 132 patients had available records of clinic BP (64 ± 13years of age). Patients with hypertension (n = 32) demonstrated a significantly greater reduction in systolic BP (-8 ± 12 versus 2 ± 9mmHg, P < 0.001) following implantation compared with normotensive patients (n = 100). Importantly, the change in BP was inversely related to baseline BP independent of age and sex following implantation of HF-SCS (n = 70, R = -0.50, P < 0.001) or LF-SCS (n = 62, R = -0.42, P = 0.001). Higher pain scores before implantation were not associated with reduction in systolic BP (R = 0.10, P = 0.43) or diastolic BP (R = -0.08, P = 0.53) (n = 69) after implantation. These findings confirm previous studies showing reduced BP following implantation of LF-SCS in patients with chronic pain and hypertension and provide novel data regarding reduced BP following implantation of newer generation HF-SCS devices.

Painful Peripheral Neuropathies of the Lower Limbs and/or Lower Extremities Treated with Spinal Cord Stimulation: A Systematic Review with Narrative Synthesis.

Painful peripheral neuropathy (PPN) is a debilitating condition with varied etiologies. Spinal cord stimulation (SCS) is increasingly used when conservative treatments fail to provide adequate pain relief. Few published reviews have examined SCS outcomes in all forms of PPN. We conducted a systematic review of SCS in PPN. The PubMed database was searched up to February 7th, 2022, for peer-reviewed studies of SCS that enrolled PPN patients with pain symptoms in their lower limbs and/or lower extremities. We assessed the quality of randomized controlled trial (RCT) evidence using the Cochrane risk of bias tool. Data were tabulated and presented narratively. Twenty eligible studies documented SCS treatment in PPN patients, including 10 kHz SCS, traditional low-frequency SCS (t-SCS), dorsal root ganglion stimulation (DRGS), and burst SCS. In total, 451 patients received a permanent implant (10 kHz SCS, n=267; t-SCS, n=147; DRGS, n=25; burst SCS, n=12). Approximately 88% of implanted patients had painful diabetic neuropathy (PDN). Overall, we found clinically meaningful pain relief (≥30%) with all SCS modalities. Among the studies, RCTs supported the use of 10 kHz SCS and t-SCS to treat PDN, with 10 kHz SCS providing a higher reduction in pain (76%) than t-SCS (38-55%). Pain relief with 10 kHz SCS and DRGS in other PPN etiologies ranged from 42-81%. In addition, 66-71% of PDN patients and 38% of nondiabetic PPN patients experienced neurological improvement with 10 kHz SCS. Our review found clinically meaningful pain relief in PPN patients after SCS treatment. RCT evidence supported the use of 10 kHz SCS and t-SCS in the diabetic neuropathy subpopulation, with more robust pain relief evident with 10 kHz SCS. Outcomes in other PPN etiologies were also promising for 10 kHz SCS. In addition, a majority of PDN patients experienced neurological improvement with 10 kHz SCS, as did a notable subset of nondiabetic PPN patients.

Utilizing 10kHz Stimulation to Salvage a Failed Low Frequency Spinal Cord Stimulation Trial.

Spinal cord stimulation (SCS) is a viable treatment option for chronic pain. One of the primary indications for SCS implantation is persistent pain after spinal surgery. Studies have demonstrated that these patients have a better response to SCS over conservative management or repeat surgery. Traditional SCS therapy uses parasthesias to overlap a patient's pain pattern and provide relief, though some patients find this uncomfortable. To avoid the use of paresthesias, a 10kHz waveform can be utilized to provide a subthreshold level of high frequency stimulation to provide superior pain relief without paresthesias. Additionally, 10kHz stimulation may be used to salvage therapy when other forms of SCS have failed. Here, we present a case in which a patient was switched from traditional SCS to 10kHz in the middle of a SCS trial with lead placement revision to salvage SCS therapy.

High-Frequency versus Low-Frequency Spinal Cord Stimulation in Treatment of Chronic Limb-Threatening Ischemia: Short-Term Results of a Randomized Trial

Introduction: The objective of the study is to determine if high-frequency (1 kHz) spinal cord stimulation (SCS) is better than low-frequency SCS for pain relief in chronic limb-threatening ischemia (CLTI). Methods: HEAL-SCS trial was designed as an open-label, parallel-group, single-center randomized study with a 1:1 allocation ratio. The trial was conducted in Meshalkin National Medical Research Center between August 2018 and February 2020. Total 56 patients underwent screening, 50 were enrolled, 6 were rejected. The participants were randomized into 2 cohorts of 25 patients each by an external coordinator using an online tool. A neurosurgeon and a vascular surgeon both examined all patients and estimated the pain intensity using visual analog scale (VAS), quality of life with short-form-36 health survey (SF-36), and functional status by walking impairment questionnaire (WIQ) at 3 and 12 months. Tissue perfusion was evaluated for 34 patients using transcutaneous oxygen tension measurement (TcPO₂) at baseline and in 12 months. Results: All 50 patients (84% men, median age 66.5 y.o) were available for primary outcome assessment 3 and 12 months after implantation. Intention-to-treat analysis demonstrated comparative advantage of HF-SCS over LF-SCS at 3 months with mean VAS score 2.8 (95% CI, 2.4; 3.2) and 3.3 (95% CI, 3.0; 3.6), respectively (p = 0.031). Clinical superiority of HF-SCS persisted at 12-month follow-up (p < 0.001). HF-SCS produced significantly greater pain relief by WIQ at 3 (p < 0.001) and 12 months (p = 0.009). Despite stair-climbing ability was better in HF-SCS group (p = 0.02), no significant difference between groups was found at 1-year post-op in terms of speed (p = 0.92) and distance scores (p = 0.68). Accordingly, the general and mental health domains of SF-36 were significantly better in HF-SCS at 12 months. Despite a tendency toward better resting oxygen pressure in HF-SCS group, there was no intergroup difference by TcPO₂ (p = 0.076). Only 1 patient (2%) required above-the-knee amputation at 10 months after LF-SCS implantation. Conclusion: High-frequency SCS provides better pain relief, life quality, and functional performance in patients with CLTI during short-term follow-up. The lack of perfusion difference between high-frequency and conventional SCS requires further examination to the possible long-term advantages of the method.

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.

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.

PO006 / #852 INHIBITORY INTERNEURON ACTIVITY IS INCREASED DURING COMBINED 10 KHZ AND LOW FREQUENCY SPINAL CORD STIMULATION: E-POSTER VIEWING

10 kHz spinal cord stimulation (SCS) is believed to operate by selectively activating inhibitory interneurons in the superficial dorsal horn without activation of dorsal column fibers. In contrast, low frequency (LF) SCS (40-60 Hz application) is believed to operate by generating action potentials in large diameter dorsal column fibers. Based on this difference in mechanisms, these types of SCS are often applied at different locations along the spinal cord, with 10 kHz SCS applied more caudally and LF SCS applied more rostrally.

Systematic Review and Network Meta-analysis of Neurostimulation for Painful Diabetic Neuropathy.

Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect comparison between SCS waveforms has been performed to date. To conduct a systematic review and network meta-analysis to evaluate the effectiveness of SCS for PDN. MEDLINE, CENTRAL, Embase, and WikiStim were searched from inception until December 2021. Randomized controlled trials (RCTs) of SCS for PDN were included. Pain intensity, proportion of patients achieving at least a 50% reduction in pain intensity, and health-related quality of life (HRQoL) data were extracted. Significant reductions in pain intensity were observed for low-frequency SCS (LF-SCS) (mean difference [MD] -3.13 [95% CI -4.19 to -2.08], moderate certainty) and high-frequency SCS (HF-SCS) (MD -5.20 [95% CI -5.77 to -4.63], moderate certainty) compared with conventional medical management (CMM) alone. There was a significantly greater reduction in pain intensity on HF-SCS compared with LF-SCS (MD -2.07 [95% CI -3.26 to -0.87], moderate certainty). Significant differences were observed for LF-SCS and HF-SCS compared with CMM for the outcomes proportion of patients with at least 50% pain reduction and HRQoL (very low to moderate certainty). No significant differences were observed between LF-SCS and HF-SCS (very low to moderate certainty). Limited number of RCTs and no head-to-head RCTs conducted. Our findings confirm the pain relief and HRQoL benefits of the addition of SCS to CMM for patients with PDN. However, in the absence of head-to-head RCT evidence, the relative benefits of HF-SCS compared with LF-SCS for patients with PDN remain uncertain.

Dorsal Column Stimulation for the Treatment of Refractory Thoracic Radiculopathy: A Case Report

Between 1996-2016, low back and neck pain expenditures amounted to $134.5 billion according to the Journal of the American Medical Association. Spinal Cord Stimulation (SCS) has been used with success in treatment of radiculopathy, peripheral nerve injury, diabetic neuropathy, failed back surgery syndrome, and complex regional pain syndrome. [1] Initially, low-frequency SCS was used and worked by activating large-diameter Ab fibers in the dorsal column, creating paresthesia stimulation at low frequency (120 Hz), high amplitude, and long duration. This was based on the Gate Control Theory so the low-rate pulsed energy applied at the certain vertebrae of the spine would activate A-beta fibers, which would gate out the nociceptive sensations carried by A-delta and C fibers. Then high-frequency stimulation was used with a frequency of 10,000 Hz, low amplitude, and short duration. This selectively activates inhibitory interneurons in the dorsal horn which suppresses wide dynamic range neurons, which are hyperactive in chronic pain. [2] High frequency stimulation has been found to be superior to low frequency in a RCT with 24 month data showing sustained relief [3].

ID:16568 Single Centre Experience With 10kHz Spinal Cord Stimulation

The use of high frequency spinal cord stimulation at 10 kHz (10kHz SCS) has been shown to be safe and effective in multiple pain aetiologies, including Failed Back Surgery Syndrome (FBSS) 1,2, Non-Surgical Refractory Back Pain (NSRBP) 3, upper limb and neck pain 4,5, failed low-frequency SCS (LF-SCS)6 and Painful Diabetic Neuropathy (PDN) 7,8. The decrease in VAS pain scores was consistent throughout the studies and the published literature suggests that 10kHz SCS is also linked with an improved quality of life and a reduction of the opioid consumption 9.

High-frequency spinal cord stimulation in treatment of chronic limb-threatening ischemia (HEAL-SCS): short-term results of a randomized trial

Background. Critical limb ischemia is defined as persistent ischemic pain attributed to a variety of severely compromised blood flow to affected extremities. The treatment of non-reconstructable critical limb ischemia is still challenging; the amputation rate was 9.3%, and mortality rate was 23.2% within 24 months. Spinal cord stimulation (SCS) has become an alternative clinical practice for the treatment of intractable pain of the extremities.Aim. To determine whether high-frequency spinal cord stimulation (SCS) is better than low-frequency SCS for pain relief in chronic limb-threatening ischemia treatment.Methods. Throughout enrollment 56 patients were examined, of whom 6 rejected to participate in the study. The participants were randomly allocated to high-frequency (HF) or low frequency (LF)-SCS groups of 25 patients each by an external statistician, using an online tool. The patients were examined by a neurosurgeon and a vascular surgeon to assess pain intensity by visual analog scale, quality of life by short-form-36 health survey (SF-36), and functional status by walking impairment questionnaire in 3 and 12 months. Tissue perfusion by transcutaneous oxygen tension measurement was also measured in 12 months.Results. Intention-to-treat analysis demonstrated comparative advantage of HF-SCS over LF-SCS in 3 months with mean visual analog scale score 2.8 [95% CI, 2.4; 3.2] and 3.3 [95% CI, 3.0; 3.6] respectively (p = 0.031). Clinical superiority of HF-SCS persisted at 12 months follow up (p&lt;0.001). HF-SCS produces significantly greater pain relief by walking impairment questionnaire in 3 (p&lt;0.001) and 12 months (p = 0.009). Accordingly, general and mental health domains of SF-36 were significantly better in HF-SCS in 12 months. Despite a tendency toward better resting oxygen pressure in HF-SCS group, there was no intergroup difference by transcutaneous oxygen tension (p = 0.076).Conclusion. High-frequency spinal cord stimulation imposes better pain relief, life quality and functional activity in patients with chronic limb-threatening ischemia in short-term follow up.

Sex-specific differences in the efficacy of traditional low frequency versus high frequency spinal cord stimulation for chronic pain

IntroductionSpinal cord stimulation (SCS), an FDA-approved therapy for chronic pain, uses paresthesia (low frequency SCS (LF-SCS)) or paresthesia-free (such as high-frequency SCS (HF-SCS)) systems, providing analgesia through partially-elucidated mechanisms, with recent studies indicating a sexual dimorphism in pain pathogenesis (Bretherton et al., Neuromodulation, 2021; Paller et al., Pain Med 10:289–299, 2009; Slyer et al., Neuromodulation, 2019; Van Buyten et al., Neuromodulation 20:642–649, 2017; Mekhail et al., Pain Pract, 2021). We aim to evaluate SCS therapy sex effects based on paradigm, utilizing visual analog scores (VAS), perceived pain reduction (PPR), and opioid use.MethodsA retrospective cohort study of SCS patients implanted between 2004 and 2020 (n = 237) was conducted. Descriptive statistics and linear mixed methods analyses were used.ResultsHF-SCS (10 kHz) was implanted in 94 patients (40 females, 54 males), and LF-SCS in 143 (70 females, 73 males). At 3 months and 6 months, HF-SCS (p < 0.001) and LF-SCS (p < 0.005) had lower VAS scores compared to baseline (p < 0.005), with no differences across groups. PPR improved in both post-implantation (p < 0.006) and at 3 months (p < 0.004 respectively), compared to baseline persisting to 6 (p < 0.003) and 12 months (p < 0.01) for HF-SCS, with significantly better PPR for HF-SCS at 3 (p < 0.008) and 6 (p < 0.001) months compared to LF-SCS. There were no differences in opioid use from baseline for either modality; however LF-SCS patients used more opioids at every time point (p < 0.05) compared to HF-SCS.VAS was improved for all modalities in both sexes at 3 months (p = 0.001), which persisted to 6 months (p < 0.05) for HF-SCS males and females, and LF-SCS females. Female HF-SCS had improved PPR at 3 (p = 0.016) and 6 (p = 0.022) months compared to baseline, and at 6 (p = 0.004) months compared to LF-SCS. Male HF-SCS and LF-SCS had improved PPR post-implantation (p < 0.05) and at 3 months (p < 0.05), with HF-SCS having greater benefit at 3 (p < 0.05) and 6 (p < 0.05) months. LF-SCS males but not females used less opioids at 6 months (p = 0.017) compared to baseline; however this effect did not persist.On linear mixed model analyses, including age, sex and stimulator type, VAS decreased with age, at each timepoint, and had a trend towards increasing with female sex, while PPR increased at 3 and 6 months and lastly HF-SCS was associated with decreased opioid use.DiscussionPPR at 3 and 6 months improved to a greater extent in HF-SCS. HF-SCS females had improved PPR at 3 and 6 months, and only LF-SCS males used less opioids at 6 months, potentially indicating sex-based pathway. Future studies should further elucidate differences in sex-based pathways and identify optimal SCS opioid-sparing paradigms for chronic pain patients.

Neuromodulation in the Treatment of Painful Diabetic Neuropathy: A Review of Evidence for Spinal Cord Stimulation.

Neuropathies, the most common complication of diabetes, manifest in various forms, including entrapments, mononeuropathies or, most frequently, a distal symmetric polyneuropathy. Painful diabetic neuropathy (PDN) in the classic "stocking" distribution is a disease of increasing prevalence worldwide and a condition for which standard medical treatment only provides modest relief. Neuromodulation offers a potential alternative to pharmacotherapies given its demonstrated efficacy in other refractory chronic neuropathic pain syndromes. High-quality evidence from randomized controlled trials (RCTs) is available in these other settings for two approaches to spinal cord stimulation (SCS): (1) conventional low-frequency SCS (LF-SCS), which modulates axonal activity in the dorsal column and is paresthesia-dependent, and (2) high-frequency SCS delivered at 10 kilohertz (10 kHz SCS), which targets neurons in the superficial dorsal horn and is paresthesia-independent. This review examines the evidence for SCS from published RCTs as well as prospective studies exploring the safety and effectiveness of treating PDN with neuromodulation. Two RCTs enrolling 60 and 36 participants with PDN showed treatment with LF-SCS reduced daytime pain by 45% to 55% for up to two years. An RCT testing 10 kHz SCS versus conventional medical management (CMM) in 216 participants with PDN revealed 76% mean pain relief after six months of stimulation. None of the studies revealed unexpected safety issues in the use of neuromodulation in this patient population. These well-designed RCTs address the unmet need for improved PDN therapies and provide data on the safety, effectiveness, and durability of SCS therapy.

Management of Chronic and Neuropathic Pain with 10 kHz Spinal Cord Stimulation Technology: Summary of Findings from Preclinical and Clinical Studies.

Since the inception of spinal cord stimulation (SCS) in 1967, the technology has evolved dramatically with important advancements in waveforms and frequencies. One such advancement is Nevro’s Senza® SCS System for HF10, which received Food and Drug and Administration (FDA) approval in 2015. Low-frequency SCS works by activating large-diameter Aβ fibers in the lateral discriminatory pathway (pain location, intensity, quality) at the dorsal column (DC), creating paresthesia-based stimulation at lower-frequencies (30–120 Hz), high-amplitude (3.5–8.5 mA), and longer-duration/pulse-width (100–500 μs). In contrast, high-frequency 10 kHz SCS works with a proposed different mechanism of action that is paresthesia-free with programming at a frequency of 10,000 Hz, low amplitude (1–5 mA), and short-duration/pulse-width (30 μS). This stimulation pattern selectively activates inhibitory interneurons in the dorsal horn (DH) at low stimulation intensities, which do not activate the dorsal column fibers. This ostensibly leads to suppression of hyperexcitable wide dynamic range neurons (WDR), which are sensitized and hyperactive in chronic pain states. It has also been reported to act on the medial pathway (drives attention and pain perception), in addition to the lateral pathways. Other theories include a reversible depolarization blockade, desynchronization of neural signals, membrane integration, glial–neuronal interaction, and induced temporal summation. The body of clinical evidence regarding 10 kHz SCS treatment for chronic back pain and neuropathic pain continues to grow. There is high-quality evidence supporting its use in patients with persistent back and radicular pain, particularly after spinal surgery. High-frequency 10 kHz SCS studies have demonstrated robust statistically and clinically significant superiority in pain control, compared to paresthesia-based SCS, supported by level I clinical evidence. Yet, as the field continues to grow with the technological advancements of multiple waveforms and programming stimulation algorithms, we encourage further research to focus on the ability to modulate pain with precision and efficacy, as the field of neuromodulation continues to adapt to the modern healthcare era.

Randomized Prospective Study in Patients With Complex Regional Pain Syndrome of the Upper Limb With High-Frequency Spinal Cord Stimulation (10-kHz) and Low-Frequency Spinal Cord Stimulation

ObjectiveThe objective of this prospective randomized study of cases and controls was to evaluate the efficacy of treatment with low-frequency spinal cord stimulation (LF-SCS) and 10 kHz spinal cord stimulation (10-kHz SCS) in patients diagnosed with complex regional pain syndrome type I (CRPS) with upper limb involvement. Materials and MethodsFifty patients were randomized to receive conventional treatment or SCS with a commercially available low-frequency or 10-kHz system. Patients were assessed at 1, 3, 6, and 12 months. The primary endpoint was at 12-months post permanent implantation of the SCS devices. Outcome measures assessed included: Numerical Rating Scale (NRS), 12-Item Short-Format Health Survey (SF-12), Oswestry Disability Index (ODI), Study Sleep Scale medical outcomes (MOS-SS), Douleur Neuropathique 4 questions pain questionnaire (DN4), Patient Global Impression Scale on the impact of treatment improvement (PGI-I), Clinician Global Impression Scale on the impact of improving the patient (CGI-I). ResultsForty-one patients were finally included in the analysis, 19 patients in the conventional treatment group, 12 in the LF-SCS group, and 10 in the 10-kHz SCS group. At the primary endpoint, patients treated with LF-SCS presented improvements in the NRS and DN4 outcomes around 2.4 and 1.5 times above the minimal clinically important difference (MCID) thresholds. At the primary endpoint, patients treated with 10-kHz SCS presented improvements in the NRS and DN4 outcomes around 2 and 1.4 times above the MCID thresholds. ConclusionsPatients experienced considerable improvement after SCS. The results show that LF-SCS has very good results when compared with conventional treatment. The results obtained with 10-kHz SCS are encouraging, with the advantages of the absence of paresthesia making it an alternative in the treatment of CRPS.

10 kHz Spinal Cord Stimulation for Treatment of Painful Diabetic Neuropathy - A Multicenter Randomized Controlled Trial

10 kHz Spinal Cord Stimulation for Treatment of Painful Diabetic Neuropathy - A Multicenter Randomized Controlled Trial