kHz Spinal Cord Stimulation Research Articles

High-Frequency 10-kHz Spinal Cord Stimulation Provides Long-term (24-Month) Improvements in Diabetes-Related Pain and Quality of Life for Patients with Painful Diabetic Neuropathy.

The SENZA-PDN study evaluated high-frequency 10-kHz spinal cord stimulation (SCS) for the treatment of painful diabetic neuropathy (PDN). Over 24 months, 10-kHz SCS provided sustained pain relief and improved health-related quality of life. This report presents additional outcomes from the SENZA-PDN study, focusing on diabetes-related pain and quality of life outcomes. The SENZA-PDN study randomized 216 participants with refractory PDN to receive either conventional medical management (CMM) or 10-kHz SCS plus CMM (10-kHz SCS + CMM), allowing crossover after six months if pain relief was insufficient. Postimplantation assessments at 24 months were completed by 142 participants with a permanent 10-kHz SCS implant, comprising 84 initial and 58 crossover recipients. Measures included the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN), Diabetes-Related Quality of Life (DQOL), Global Assessment of Functioning (GAF), and treatment satisfaction. Over 24 months, 10-kHz SCS treatment significantly reduced pain severity by 66.9% (P < .001; BPI-DPN) and pain interference with mood and daily activities by 65.8% (P < .001; BPI-DPN). Significant improvements were also observed in overall DQOL score (P < .001) and GAF score (P < .001), and 91.5% of participants reported satisfaction with treatment. High-frequency 10-kHz SCS significantly decreased pain severity and provided additional clinically meaningful improvements in DQOL and overall functioning for patients with PDN. The robust and sustained benefits over 24 months, coupled with high participant satisfaction, highlight that 10-kHz SCS is an efficacious and comprehensive therapy for patients with PDN.

ID: 337285 Comparing 10kHz Spinal Cord Stimulation Efficacy in Persistent Spinal Pain with versus without Previous Surgery

ID: 337285 Comparing 10kHz Spinal Cord Stimulation Efficacy in Persistent Spinal Pain with versus without Previous Surgery

ID: 330673 Improved Quality of Life with 10kHz Spinal Cord Stimulation Therapy for Nonsurgical Refractory Back Pain

ID: 330673 Improved Quality of Life with 10kHz Spinal Cord Stimulation Therapy for Nonsurgical Refractory Back Pain

ID: 333441 Characterization of strength-frequency-train curve of 10kHz spinal cord stimulation

ID: 333441 Characterization of strength-frequency-train curve of 10kHz spinal cord stimulation

ID: 328468 10kHz Spinal Cord Stimulation Improves Metrics of Spinal Sensory Processing in a Diabetic Rodent Model

ID: 328468 10kHz Spinal Cord Stimulation Improves Metrics of Spinal Sensory Processing in a Diabetic Rodent Model

ID: 337631 Benefits of Direct-to-Implant for High-Frequency 10 kHz Spinal Cord Stimulation

ID: 337631 Benefits of Direct-to-Implant for High-Frequency 10 kHz Spinal Cord Stimulation

ID: 333942 A Prospective Study of 10 kHz Spinal Cord Stimulation in Patients who Failed Traditional SCS

ID: 333942 A Prospective Study of 10 kHz Spinal Cord Stimulation in Patients who Failed Traditional SCS

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.

10 kHz spinal cord stimulation improves metrics of spinal sensory processing in a male STZ rat model of diabetes

To explore why clinical 10 kHz spinal cord stimulation (10 kHz SCS) might improve neurological function in a model of painful diabetic neuropathy (PDN), the short-term behavioral, electrophysiological, and histological effects of 10 kHz SCS were studied using adult male streptozotocin (STZ)-induced diabetic Sprague-Dawley rats. Four testing groups were established: Naïve controls (N = 8), STZ controls (N = 7), STZ+Sham SCS (N = 9), and STZ+10 kHz SCS (N = 11). After intraperitoneal injection (60 mg/kg) of STZ caused the rats to become hyperglycemic, SCS electrodes were implanted in the dorsal epidural space over the L5-L6 spinal segments in the STZ+Sham SCS and STZ+10 kHz SCS groups and were stimulated for 14 days. The von Frey filament paw withdrawal threshold was measured weekly. At termination, animals were anesthetized and the electrophysiologic response of dorsal horn neurons (receptive field size, vibration, radiant warmth) of the ipsilateral foot was measured. Tissue from the plantar paw surface was obtained post-euthanization for intraepidermal nerve fiber density measurements. In comparison to other control groups, while no significant effect of 10 kHz SCS on peripheral intraepidermal nerve fiber density was observed, 10 kHz SCS ‘normalized’ the central neural response to vibration, receptive field, and paw withdrawal threshold, and elevated the neural response to tissue recovery from warm stimuli. These results suggest that short-term, low intensity 10 kHz SCS operates in the spinal cord to ameliorate compromised sensory processing, and may compensate for reduced peripheral sensory functionality from chronic hyperglycemia, thereby treating a broader spectrum of the sensory symptoms in diabetic neuropathy.

127 Durable Treatment of Painful Diabetic Neuropathy With 10 kHz Spinal Cord Stimulation

INTRODUCTION: Approximately 25% of people with diabetes experience painful diabetic neuropathy (PDN), but conventional medical management (CMM) is ineffective for many patients. We previously presented partial study results showing that high-frequency (10 kHz) spinal cord stimulation (SCS) provides substantial symptom relief. Here we report full study results through 24-month (24M) follow-up. METHODS: We conducted a multicenter RCT to evaluate 10 kHz SCS in PDN patients. Key study inclusion criteria were: PDN symptoms = 12M refractory to medications, lower limb pain intensity = 5cm (0-10 cm visual analog scale [VAS]), and hemoglobin A1c = 10%. Patients (n = 216) were randomized 1:1 to 10 kHz SCS plus CMM or CMM alone, with optional treatment crossover at 6M. RESULTS: Patients randomized to 10 kHz SCS experienced significantly greater pain relief at 6M than those treated with CMM alone (p &lt; 0.001). For all patients who received 10 kHz SCS, at 24M post-implantation the average pain relief was 80% from pre-implantation (p &lt; 0.001), and the treatment responder rate was 90%. Clinician-assessed sensory function showed significant improvements with 10 kHz SCS. At 6M, 59% of patients treated with 10 kHz SCS had sensory improvement versus 9% of those treated with CMM alone (p &lt; 0.001). At 24M, 10 kHz SCS improved sensory function for 65% of patients. Patients receiving 10 kHz SCS also experienced significant improvements in health-related quality of life (HRQoL, p &lt; 0.001). At 24M, the mean HRQoL improvement was 2.9-4.8 times the minimum clinically important difference for patients with type 2 diabetes. CONCLUSIONS: The results demonstrate that 10 kHz SCS provides significant, durable reductions in pain and improvements in sensory function and HRQoL. Sensory function improvements support the unique disease-modifying potential of 10 kHz SCS.

Healthcare Utilization (HCU) Reduction with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Therapy.

Spinal cord stimulation (SCS) is a well-established treatment for patients with chronic pain. With increasing healthcare costs, it is important to determine the benefits of SCS in healthcare utilization (HCU). This retrospective, single-center observational study involved 160 subjects who underwent implantation of a high-frequency (10 kHz) SCS device. We focused on assessing trends in HCU by measuring opioid consumption in morphine milligram equivalents (MME), as well as monitoring emergency department (ED) and office visits for interventional pain procedures during the 12-month period preceding and following the SCS implant. Our results revealed a statistically significant reduction in HCU in all domains assessed. The mean MME was 51.05 and 26.52 pre- and post-implant, respectively. There was a 24.53 MME overall decrease and a mean of 78.2% statistically significant dose reduction (p < 0.0001). Of these, 91.5% reached a minimally clinically important difference (MCID) in opioid reduction. Similarly, we found a statistically significant (p < 0.01) decrease in ED visits, with a mean of 0.12 pre- and 0.03 post-implant, and a decrease in office visits for interventional pain procedures from a 1.39 pre- to 0.28 post-10 kHz SCS implant, representing a 1.11 statistically significant (p < 0.0001) mean reduction. Our study reports the largest cohort of real-world data published to date analyzing HCU trends with 10 kHz SCS for multiple pain etiologies. Furthermore, this is the first and only study evaluating HCU trends with 10 kHz SCS by assessing opioid use, ED visits, and outpatient visits for interventional pain procedures collectively. Preceding studies have individually investigated these outcomes, consistently yielding positive results comparable to our findings.

Treatment of Painful Diabetic Neuropathy with 10 kHz Spinal Cord Stimulation: Long-Term Improvements in Hemoglobin A1c, Weight, and Sleep Accompany Pain Relief for People with Type 2 Diabetes.

The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D). This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (>7% and >8%) and body mass index (BMI; ≥30 and ≥35 kg/m2). At 24 months, participants with preimplantation HbA1c >7% and >8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥30 and ≥35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts. This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief. ClincalTrials.gov Identifier, NCT03228420.

Spinal cord stimulation in painful diabetic neuropathy: An overview

Up to 25% of people with diabetes develop painful diabetic neuropathy (PDN). The standard of care pharmacotherapies for PDN have limited efficacy with a considerable side effect profile. Spinal cord stimulation (SCS) is a form of electrical neurostimulation that modulates neural function via electrodes implanted into the spinal epidural space. While low frequency SCS has been shown to be potentially effective for treating pain associated with neuropathies, it masks pain perception by inducing paresthesia. Compared to low frequency SCS, high frequency (10 kHz) SCS delivers paresthesia-free therapy. As was shown in a randomized controlled trial, SENZA-PDN (NCT03228420), 10 kHz SCS is safe and effective for the treatment of painful diabetic neuropathy. 10 kHz SCS offered a comprehensive treatment that improved pain levels, sleep, quality of life, and neurological function. These improvements correlated with a high degree of patient satisfaction. 10 kHz SCS provides a safe, durable and effective treatment for PDN with the unique potential to improve neurological function. In patients for whom durable, effective treatments have been limited thus far, the findings of the SENZA-PDN study are encouraging.

Real-world outcomes in spinal cord stimulation: predictors of reported effect and explantation using a comprehensive registry-based approach.

Despite advancements in implanted hardware and development of novel stimulation paradigms in Spinal Cord Stimulation (SCS), real world evidence suggests a large variation in patient reported outcomes and a proportion of patients are later explanted due to loss of analgesia. Possible predictors for outcome have been explored in smaller short-term evaluations, but few clinically applicable robust measures for long term outcome have emerged. We performed a comprehensive retrospective study based on an assembled patient-level aggregated database from multiple local and national registries in Sweden. Variables associated with risk of explantation (due to insufficient analgesia) and analgesic effect was analyzed using a Cox regression analysis and an ordered logit regression model, respectively. We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes. This study suggests that a higher educational level and being employed are associated with successful treatment outcome in patients with chronic pain treated with SCS in Sweden.

Model-based analysis of subthreshold mechanisms of spinal cord stimulation for pain

Objective. Spinal cord stimulation (SCS) is a common treatment for chronic pain. For decades, SCS maximized overlap between stimulation-induced paresthesias and the patient’s painful areas. Recently developed SCS paradigms relieve pain at sub-perceptible amplitudes, yet little is known about the neural response to these new waveforms or their analgesic mechanisms of action. Therefore, in this study, we investigated the neural response to multiple forms of paresthesia-free SCS. Approach. We used computational modeling to investigate the neurophysiological effects and the plausibility of commonly proposed mechanisms of three paresthesia-free SCS paradigms: burst, 1 kHz, and 10 kHz SCS. Specifically, in C- and Aβ-fibers, we investigated the effects of different SCS waveforms on spike timing and activation thresholds, as well as how stochastic ion channel gating affects the response of dorsal column axons. Finally, we characterized membrane polarization of superficial dorsal horn neurons. Main results. We found that none of the SCS waveforms activate nor modulate spike timing in C-fibers. Spike timing was modulated in Aβ-fibers only at suprathreshold amplitudes. Ion channel stochasticity had little effect on Aβ-fiber activation thresholds but produced heterogeneous spike timings at suprathreshold amplitudes. Finally, local cells were preferentially polarized in their axon terminals, and the magnitude of this polarization was dependent on cellular morphology and position relative to the stimulation electrodes. Significance. Overall, the mechanisms of action of subparesthetic SCS remain unclear. Our results suggest that no SCS waveforms directly activate C-fibers, and modulation of spike timing is unlikely at subthreshold amplitudes. We conclude that potential subthreshold neuromodulatory effects of SCS on local cells are likely to be presynaptic in nature, as axons are preferentially depolarized during SCS.

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

AimsTo evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). MethodsThe SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant’s well-being and was attributable to a neurological finding. ResultsAt 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. ConclusionsOver 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN.Trial Registration: ClincalTrials.gov Identifier, NCT03228420.

1809-PUB: Painful Diabetic Neuropathy—Patients Treated with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Experience Significant Reductions in A1C and Weight

Objective: Up to 9 million Americans have painful diabetic neuropathy (PDN), which can be debilitating. For PDN patients, 10 kHz SCS has been shown to provide mean pain relief of 77% at 24 months (24M), and here we report secondary, novel potential benefits for A1C and body weight. Methods: Subjects received a 10 kHz SCS implant plus medical management for their pain and diabetes. Subjects were followed for 24M post-implantation. Key inclusion criteria were: PDN ≥12M refractory to medications, lower limb pain ≥5cm (10cm VAS), and A1C ≤10%. For T2D subjects, changes in weight were evaluated for all subjects and cohorts with pre-implant BMI ≥30 and ≥35, and changes in A1C were evaluated for cohorts with pre-implant A1C ≥7.0% and ≥8.0%. Results: For cohorts evaluated, A1C and weight generally decreased with time (Fig. 1). For subjects with pre-implant A1C ≥8.0%, the mean A1C reduction was 0.52% at 6M (p=0.064) and 1.04% at 24M (p=0.007). For all subjects, the mean weight reduction was 1.8 kg at 12M (p=0.058) and 3.1 kg at 24M (p=0.003). For subjects with pre-implant BMI ≥35, the mean weight reduction was 5.4 kg at 24M (p=0.005). Conclusions: Previously reported pain relief and sensory improvement, coupled with reductions in A1C and weight reported here, further demonstrate the benefits of 10 kHz SCS treatment in the comprehensive care of T2D patients with PDN. Disclosure D.C.Klonoff: Consultant; EOFlow Co., Ltd., Fractyl Health, Inc., Integrity, Lifecare, Inc., Rockley Photonics, Thirdwayv Inc. B.L.Levy: Advisory Panel; Nevro Corp., CeQur SA, Consultant; Nevro Corp., CeQur SA, Digma Medical. M.Jaasma: Consultant; Bone Health Technologies, Inc., Employee; Nevro Corp., Bone Health Technologies, Inc. M.Bharara: Employee; Nevro Corp. C.E.Nasr: Advisory Panel; Siemens, Horizon Therapeutics plc. D.L.Caraway: Employee; Nevro Corp. E.Petersen: Consultant; Abbott, Biotronik, Medtronic, Nalu, Nevro Corp., Presidio Medical, Saluda Medical, Vertos Medical Inc., Research Support; Nalu, Nevro Corp. D.G.Armstrong: Research Support; Medaxis LLC. Funding Nevro Corp.

481-P: 10kHz SCS Restores Mechanical and Thermal Neural Processing in a Rodent Model of Painful Diabetic Neuropathy

A recent randomized controlled trial of 10 kHz spinal cord stimulation (SCS) in patients with painful diabetic neuropathy (PDN) has demonstrated significant and durable improvements in neurologic status, particularly sensory restoration of the foot (Petersen et al 2021, Argoff et al 2023). In order to gain further mechanistic insight into the improvements in sensory processing by 10kHz SCS, we analyzed the receptive field (RF) size and responses of spinal dorsal horn (DH) neurons to mechanical and thermal stimuli of the paw in a PDN rat model. For PDN-model, Rats were given a single effective dose of streptozotocin (STZ), while Naïve animals were injected with 0.9% saline. Four groups were studied: Naïve, STZ, STZ+ShamSCS, and STZ+10kHzSCS. Rats were anesthetized with urethane and a laminectomy was performed for DH neurons recording. We analyzed RF size and the response of DH neurons to vibrotactile stimulation and thermal sensation. Both the Naïve and STZ+10kHzSCS groups had significantly smaller RFs than the STZ Control and STZ+ShamSCS groups. In response to a 1 Hz vibration frequency, Naïve and STZ+10kHzSCS groups had higher peak power spectral density (PSD) of DH firing than STZ+ShamSCS, and PSD for the STZ+10kHzSCS group was statistically higher than for the STZ Control group. Response of DH neurons showed no significant differences between groups during the thermal stimulation, but the post-stimulus firing rates for the STZ+10kHzSCS group were significantly higher compared to STZ Control and STZ+ShamSCS. These data suggest that 10 kHz SCS amplified the DH response to large fiber (vibration) and small fiber (warm) signals and normalized the receptive field of the paw (acuity) in PDN rats. In diabetes, where peripheral sensory compromise from chronic hyperglycemia can lead to loss of protective sensation, such ‘tuned amplification’ as provided by 10 kHz SCS in the central nervous system may compensate for the reduced functionality seen in the peripheral sensory systems. Disclosure K.Lee: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. D.Wang: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.

482-P: Behavioral Assessment of 10kHz Spinal Cord Stimulation–Mediated Pain Relief in a Rat Model of Painful Diabetic Neuropathy

Painful diabetic neuropathy (PDN) is a serious complication of diabetes and occurs in approximately 20% of diabetic patients. In a recent RCT, 10kHz spinal cord stimulation (10kHz SCS) was shown to be a promising therapy for PDN, in both pain reduction and possible neurological improvements (Petersen et al 2021). In this study, we aimed to observe the behavioral effects of 10kHz SCS on PDN using streptozotocin (STZ)-induced diabetic rats. We established four testing groups: Naïve controls, STZ controls, STZ+Sham SCS, and STZ+10kHz SCS. A single effective dose (60 mg/kg) of the cytotoxic agent STZ caused the rats to become hyperglycemic within 72 hours and lasted for several weeks. These STZ-injected rats also showed a significant and continuous reduction in body weight in comparison to Naïve control rats. Using the von Frey test for mechanical allodynia, we observed that 14 days of 24h/day low-intensity (30% of motor threshold) 10kHz SCS significantly elevated the mechanical pain withdrawal thresholds compared to STZ controls or STZ+Sham SCS animals, reaching statistical equivalence to Naïve controls. In a thermal preference assay, all animals exhibited a training effect towards less activity and more preference to the room temperature side vs the non-painful heat side of a two-temperature chamber over the several-week protocol. We found that STZ-injected animals demonstrated significantly less exploration activity in the 10min testing periods compared to Naïve controls but neither the thermal preference nor the total distance they traveled were restored after 14 days of 10kHz SCS. Our results demonstrate that 10 kHz SCS resulted in behavioral outcomes reflective of the mechanical pain reduction in the PDN rodent model. These findings provide supporting evidence for the recent RCT data and underscore the conclusion that 10kHz SCS can effectively treat patients with refractory PDN. Disclosure D.Wang: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. K.Lee: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.

ID: 216418 Activation of Inhibitory Circuit in Reflex Motor Pathways by 10kHz Versus Single Pulse/Low Frequency SCS

High frequency (10kHz) spinal cord stimulation (SCS) is a well-established and expanding neuromodulatory technique for treating chronic pain. Despite clinical success, the cellular mechanisms of 10kHz SCS for activating neurons is still not fully understood. In previous preclinical work, we reported that 10kHz SCS activated the thigh muscle selectively, with very little activation by single pulse (low frequency) SCS. The toe muscle showed a similar but opposite selectivity, where single pulse/low frequency SCS resulted in more selective activation of the toe than 10kHzSCS. In the literature, both animal and human studies reported that use of a paired pulse protocol generates recurrent, presynaptic inhibition and homosynaptic depression depending on the delay between first and second pulses. Here we studied the activation of inhibitory circuits in reflex motor pathways using a paired pulse protocol of 10 kHz SCS vs. low frequency/single pulse SCS.