High Frequency Spinal Cord Stimulation Research Articles

Long-term Efficacy and Safety of High-frequency Spinal Stimulation for Chronic Pain: A Meta-analysis of Randomized Controlled Trial.

The aim of our meta-analysis was to systematically assess the enduring effectiveness and safety of high-frequency spinal stimulation (HF-SCS) in the management of chronic pain. We developed a comprehensive literature search strategy to identify clinical trials investigating the efficacy of high-frequency spinal stimulation for chronic pain. The search was conducted in multiple databases, including Web of Science, Cochrane, PubMed, and Embase, covering the period from 2004 to 2023. The inclusion and exclusion criteria established for this study were applied to screen the eligible literature by carefully reviewing abstracts and, when necessary, examining the full text of selected articles. To assess the quality of the included studies, we utilized the risk of bias assessment tool provided by the Cochrane Collaboration.The PRISMA method was followed for the selection of articles, and the quality of the articles was evaluated using the risk assessment table for bias provided by the Cochrane Collaboration.Meta-analysis of the selected studies was performed using Review Manager 5.4 and STATA 16.0. Effect sizes for continuous data were reported as mean differences (MD) or standardized mean differences (SMD), while categorical data were analyzed using relative risks (RR). According to our predefined literature screening criteria, a total of seven English-language randomized controlled trials (RCTs) were included in the meta-analysis. The findings from the meta-analysis demonstrated that high-frequency spinal cord stimulation (HF-SCS) exhibited superior efficacy in the long-term treatment of chronic pain when compared to the control group (RR = 2.44, 95% CI [1.20, 4.96], P = 0.01). Furthermore, HF-SCS demonstrated a statistically significant improvement in the Oswestry Disability Index score (mean difference MD = 3.77, 95% CI [1.17, 6.38], P = 0.005).However, for pain assessment (standardized mean difference SMD = -0.59, 95% CI [-1.28, 0.10], P = 0.09), Patient Global Impression of Improvement (PGI-I) score (MD = 0.11, 95% CI [-0.66, 0.88], P = 0.78 for 6 months; MD = 0.02, 95% CI [-0.42, 0.43], P = 0.97 for 12 months), Clinical Global Impression of Improvement (CGI-I) score (MD = -0.58, 95% CI [-1.62, 0.43], P = 0.27 for 6 months; MD = -0.23, 95% CI [-0.94, 0.48], P = 0.52 for 12 months), and occurrence of adverse effects (odds ratio OR = 0.77, 95% CI [0.23, 2.59], P = 0.67) from a statistical point of view, HF-SCS did not show sufficient effect compared with the control group. Not significant enough to consider it. The findings from our comprehensive review and meta-analysis, encompassing research from 2004 to 2023, offer encouraging data about the prolonged efficacy and safety of HF-SCS in chronic pain management. Nonetheless, recognizing the constraints of the existing evidence is crucial. Upcoming clinical trials, meticulously planned and stringent, are essential to bolster the current body of evidence and reach more conclusive findings.

346 Durable Responses at 24 Months With High-Frequency Spinal Cord Stimulation for Nonsurgical Refractory Back Pain

INTRODUCTION: Chronic refractory back pain causes significant disability and is one of the most common reasons for patients seeking health care. Few treatment options exist for chronic back pain patients who have failed conventional medical management (CMM) and who have not had and are not candidates for spine surgery, a condition we refer to as non-surgical refractory back pain (NSRBP). METHODS: Patients with NSRBP were evaluated after 1:1 randomization to 10kHz SCS plus CMM or CMM alone. Primary endpoint and secondary endpoints were assessed, and optional crossover was allowed at 6 months, with observational follow-up over 12 months (Kapural, 2022). All patients treated with 10kHz SCS were eligible for follow-up through 24 months after implantation. Outcomes included pain, Oswestry Disability Index (ODI), quality-of-life (EQ-5D-5L), 3-item Pain Sleep Questionnaire (PSQ-3), opioid use, patient’s global impression of change (PGIC), and safety. RESULTS: Of the 125 patients who received a permanent implant, 121 completed 12-month follow-up, 101 reconsented for extended follow-up, and 98 completed 24-month follow-up. At 24 months after implantation 82% achieved =50% pain relief. All outcome measures improved by at least double the minimal clinically important difference. Ninety-percent of patients met at least one of the multidimensional outcomes. Of those who reported opioid use during the study, and 62% of decreased or stopped. Through 24 months, 3 of 125 (2.4%) devices were explanted due to patient dissatisfaction with SCS therapy. CONCLUSIONS: The addition of 10kHz SCS to CMM in patients with NSRBP offers profound improvements at 24 months in pain, function, quality-of-life, and reduced opioid use. This study provides much-needed evidence to inform current clinical practice for managing patients with NSRBP.

894 Comparison of Intraoperative Neural Changes During Tonic Versus High-Frequency Spinal Cord Stimulation in Chronic Pain Patients

INTRODUCTION: Chronic pain is a prevalent issue that may affect up to 34% of US adults, and spinal cord stimulation (SCS) is a promising therapy. However, SCS device selection remains a challenge because there are currently no objective biomarkers to evaluate chronic pain, or to predict which patients will be responders. METHODS: Intraoperative EEG signals were recorded in 24 chronic pain patients (14 women) during permanent SCS electrode placement surgery. Neural responses were captured with respect to tonic (60 Hz/300 µs) and high-frequency (1 kHz/30 µs) SCS paradigms in a randomized manner and correlated to Numeric Rating Scale (NRS) scores. All data were analyzed offline in MATLAB and SPSS v28.0.1.1. RESULTS: Our analyses for the main effects demonstrated a significant difference between cortical regions (F(2.88,57.7) = 7.60 , p < 0.001) and a marginal difference between stimulation conditions (F(2,40) = 2.970, p = 0.063). The post hoc analysis for these factors revealed that alpha/theta peak power ratio was significantly different between in central regions (C3-C4) between tonic and HF stimulation (p = 0.006) and temporal regions (T3-T4) between baseline and HF stimulation (p = 0.049). The comparison of NRS scores before and 3 months after surgery indicated a significant improvement in pain intensity (p < 0.001) at the group level. The neural features found to be significantly correlated with preoperative NRS scores in PFC (p = 0.036 and p = 0.025) and temporal regions (p = 0.041 and p = 0.012) under both stimulations. CONCLUSIONS: Our preliminary results support the possibility that different stimulation patterns affect the electrophysiological activity differently in various cortical regions. Such differences might account for the variability in pain suppression in patients with chronic pain treated with SCS. Future work will utilize this dataset to develop a machine learning classifier to support objective device selection strategies.

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.

A single-center real-world review of 10 kHz high-frequency spinal cord stimulation outcomes for treatment of chronic pain

ObjectiveTo compare pragmatic real-world 10-kHz high-frequency spinal cord stimulation (HF-SCS) outcomes at a single academic center to the industry-sponsored SENZA-RCT and Stauss et al. study. MethodsThis single-center retrospective study included patients with refractory back or limb pain trialed and/or permanently implanted with the Nevro HF-SCS system from 2016 to 2021. Demographic and outcome data were obtained from the electronic medical record (EMR) and real-world global database maintained by Nevro Corp. Data obtained from the global database were confirmed using the EMR. Main outcome measures included positive responder status (≥50% patient-reported percentage pain reduction (PRPPR)), improvement in function, improvement in sleep, and reduction in pain medication usage. Comparison groups included patient outcomes from the SENZA-RCT and Stauss et al. study. ResultsPatients (N = 147) trialed with HF-SCS were reviewed, with data available for 137. Positive trialed patient responder rate (≥50% PRPPR) was 77% (106/137, 95CI 70–84%) vs. 87% (1393/1607, 95CI 85–89%) Stauss et al. vs. 93% (90/97, 95CI 88–98%) SENZA-RCT HF-SCS. At the last available follow-up, positive implanted patient responder rate was 73% (58/80, 95CI 63–82%) vs. 78% (254/326, 95CI 73–82%) Stauss et al. vs. 79% (71/90, 95CI 70–87%) SENZA-RCT HF-SCS. Sixty-seven percent (59/88, 95CI 57–77%) reported improved function vs. 72% (787/1088, 95CI 70–75%) Stauss et al.; 45% (31/69, 95CI 33–57%) reported improved sleep vs. 68% (693/1020, 95CI 65–71%) Stauss et al. and 16% (9/56, 95CI 6–26%) reported decrease in medication use vs. 32% (342/1070, 95CI 29–35%) Stauss et al. ConclusionPatient responder rates in this retrospective pragmatic real-world study of HF-SCS are consistent with previous industry-sponsored studies. However, improvements in quality-of-life measures and reduction in medication usage were not as robust as reported in industry-sponsored studies. The findings of this non-industry-sponsored, independent study of HF-SCS complement those of previously published studies by reporting patient outcomes collected in the absence of industry sponsorship.

Conventional management and current guidelines for painful diabetic neuropathy

Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant curtailment of functionality and quality of life. Patients may present with unremitting burning, aching or “electric-shock” type pains in their feet, legs and later, in the hands. Conventional management approaches must focus not only on pain relief, but also on concurrent sleep problems, mood disorders and functionality. The mainstay of treatment is pharmacotherapy. Most current international guidelines recommend a choice of four drugs: amitriptyline, duloxetine, pregabalin or gabapentin, as initial treatment for PDN. Recent evidence from the OPTION-DM trial demonstrated that these drugs and their combinations have equivalent efficacy. Moreover, combination treatment provided significant pain relief to patients with inadequate response to the maximum tolerated dose of monotherapy. PDN refractory to pharmacotherapy can be treated with capsaicin 8% or high frequency spinal cord stimulation.

Real world outcomes with spinal cord stimulation

High frequency spinal cord stimulation (SCS) is a safe and effective treatment option for refractory painful diabetic neuropathy and should be considered for use early in the course of the disease. Raising awareness of this minimally invasive treatment option among physician networks is of major importance.

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.

ID: 222114 Effects of High Frequency Spinal Cord Stimulation as Measured by Autonomic Tone and fMRI

We investigated high frequency spinal cord stimulation (HF-SCS) efficacy in 1) reducing autonomic output as measured by galvanic skin response (GSR) levels during anticipation of and exposure to noxious thermal stimuli in while undergoing functional magnetic resonance imaging of the brain, and 2) altering subjective experience of pain as measured by the Short Form McGill Pain Questionnaire (SF-MPQ-2) and a modified Brief Pain Inventory Short Form (BPI-SF).

ID: 217111 Use of High Frequency Spinal Cord Stimulation to Treat Monoclonal Antibody Induced Neuropathy: Case Report

The use of spinal cord stimulators (SCS) in the treatment of painful diabetic peripheral neuropathy is well-described in medical literature1,2. However, the efficacy of SCS to treat other peripheral neuropathic pain states is not well described. In this case study, we report the use of a high frequency SCS system to treat monoclonal antibody-induced peripheral neuropathy.

ID: 216535 Ten-Year Real-World Data on the Efficacy of High-Frequency 10 kHz Spinal Cord Stimulation

The efficacy of high frequency spinal cord stimulation (10 kHz SCS) for the treatment of chronic trunk and or limb pain has been demonstrated by the SENZA-RCT1 study. Real world data with a 12-month follow-up additionally support the efficacy of 10kHz SCS2. Previous work also demonstrated long-term durability of 10 kHz SCS and clinically meaningful results for patients with chronic lower back and or leg pain at 24 months (SENZA-EU)3. Here we present 10-year follow-up data on patients who originally participated in the SENZA-EU study3 and continued with usual care in a real-world setting over a mean period of 10 years.

ID: 216388 Treatment of Post-Surgical Pain Following Mastectomy With 10 kHz Spinal Cord Stimulation: A Case Study

Post-surgical pain (PSP) following mastectomy is often neuropathic1 and focally located around the chest wall, armpit and or arm2. High-frequency spinal cord stimulation (10kHz SCS) could potentially be used as a treatment option for this indication as pre-clinical evidence for 10kHz SCS demonstrates an inhibitory effect of interneurons in the dorsal horn providing a useful mechanism of action (MOA) for paresthesia-free neuropathic pain relief3. Here we present a case study detailing the successful use of 10kHz SCS in the treatment of PSP following mastectomy.

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.

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: 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.

ID: 200637 10 kHz SCS Provides Durable Pain Relief for Patients With Painful Diabetic Neuropathy

Approximately 37 million Americans have diabetes,1 with ∼25% experiencing painful diabetic neuropathy (PDN).2 Unfortunately, conventional medical management (CMM), which includes pharmacotherapies, is largely ineffective for many patients.2 High-frequency (10 kHz) spinal cord stimulation (SCS) has been shown to provide substantial symptom relief for PDN,3 and here we report durability of outcomes to 24 months (24M).

ID: 216932 High-Frequency Spinal Cord Stimulation Salvages Therapy in Failed Low-Frequency Treatment of Failed Back Surgery Syndrome

Spinal cord stimulator (SCS) is a Federal Drug Administration-approved treatment modality for treating failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), and diabetic neuropathy (DN). Patients first must undergo an SCS trial by placing electrodes in the epidural space with a temporary external power source to determine if the patient achieves pain relief. The pulses generated by the SCS create paresthesias to interfere with the pain. If the trial is successful, a permanent SCS is implanted. Despite using paresthesias in low-frequency SCS treatment, many patients find this uncomfortable. To avoid using paresthesias with low frequency, a newer, higher frequency version using a waveform of 10 kHz at a subthreshold level can provide superior pain relief without paresthesias. Additionally, high-frequency SCS may be used to salvage therapy where low-frequency SCS has failed. Here, we present a case where we switched mid-trial from low-frequency to high-frequency SCS with lead placement revision salvaging the trial and improving the patient’s overall pain.

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.

Effects of Stimulus Pattern on Inspiratory Muscle Activation during High Frequency Spinal Cord Stimulation in an Animal Model

Background: High Frequency Spinal Cord Stimulation (HF-SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. Objective: To evaluate the pattern of diaphragm (D), parasternal (PA) and external intercostal (EI) activation during rectangular vs ramp-shape HF-SCS, compared to spontaneous breathing. Methods: In 8 anesthetized dogs, a stimulating disc electrode was positioned on the ventral surface of the spinal cord at the T2 level. Stimulus train duration for ramp-shape and rectangular HF-SCS was set at 1.3s since this duration approximated that occurring during spontaneous breathing. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes approximated that occurring during SB. The ramp-shape pattern of stimulation was linearly increased from zero to the desired stimulus amplitude. Single motor unit (SMU) EMG activity of the PA, EI and D muscles was assessed during SB and HF-SCS (following spinalization at the C2 level) with rectangular and ramp-shape stimulation patterns, in separate trials. Time of onset (To), b) time to peak discharge frequency (TTP) and c) peak firing frequency (PFF) were measured under each condition. To and TTP were determined relative to the onset of inspiratory flow and expressed as a percentage of inspiratory time (Ti). The patterns of the inspiratory muscle activation during HF-SCS were compared to that obtained during spontaneous breathing. Results: During SB, D was recruited first followed by PA and EI; mean ± SE To was 19.6±1.4, 32.1±2.4 and 40.4±2.3%Ti, respectively. During rectangular HF-SCS, To was 3.0±0.4, 5.8±1.2 and 4.3±0.9%Ti for D, PA and EI, respectively (p&lt;0.05 for each compared to SB). During ramp-shape HF-SCS, To was 23.1±3.7, 33.6±4.5 and 39.9±4.6%Ti for D, PA and EI respectively (NS for each compared to SB). During SB, TTP was 65.2±2.2, 71.0±2.0 and 74.0±2.0%Ti for D, PA and EI. During rectangular HF-SCS, TTP was 30.4±3.7, 25.4±3.3 and 35.2±2.8%Ti, for D, PA and EI (p&lt;0.05 for each compared to SB). During ramp-shape HF-SCS, TTP was 60.5±2.9, 58.2±2.7 and 62.6±6.0%Ti for Dia, PA and EI (p&lt;0.05 for PA and EI compared to SB). During SB, PFF of SMUs of the D, PA and EI were 10.3±0.5, 12.8±0.4 and 12.2±0.7Hz, respectively. However, during rectangular HF-SCS, PFF were 14.0±0.6, 14.7±0.7 and 14.5±0.5Hz for D, PA and EI, respectively (p&lt;0.05 for each compared to SB). During ramp-shape HF-SCS, PFF were 12.3±0.8, 13.8±0.9 and 12.6±1.2 for D, PA and EI, respectively (NS for each compared to SB). Conclusion: Activation of the inspiratory motoneuron pools via HF-SCS is receptive to different patterns of electrical stimulation.Ramp-shape HF-SCS compared to rectangular HF-SCS results in a more physiologic pattern of inspiratory muscle activation. National Institutes of Health grant no. R01 NS105785. Conflict of interest: Dr. A. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems (nos. 5,678,535 and 5,911,218). Dr. A. DiMarco and Dr. K. Kowalski hold the U.S. patents for technology related to the content of this study, Respiratory Muscle Activation by Spinal Cord Stimulation (no. 8,352,036). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

In Vivo Measurements Reveal that Both Low- and High-frequency Spinal Cord Stimulation Heterogeneously Modulate Superficial Dorsal Horn Neurons

Current sub-perception spinal cord stimulation (SCS) is characterized by the use of high-frequency pulses to achieve paresthesia-free analgesic effects. High-frequency SCS demonstrates distinctive properties from paresthesia-based SCS, such as a longer time course to response, implying the existence of alternative mechanism(s) of action beyond gate control theory. We quantified the responses to SCS of single neurons within the superficial dorsal horn (SDH), a structure in close proximity to SCS electrodes, to investigate the mechanisms underlying high-frequency SCS in 62 urethane-anesthetized male rats. Sciatic nerve stimulation was delivered to isolate lumbar SDH neurons with evoked C-fiber activity. The evoked C-fiber activity before and after the application of SCS was compared to quantify the effects of SCS across stimulation intensity and stimulation duration at three different stimulation frequencies. We observed heterogeneous responses of SDH neurons which depended primarily on the type of unit. Low-threshold units with spontaneous activity, putatively inhibitory interneurons, tended to be facilitated by SCS while the other unit types were suppressed. The effects of SCS were more prominent with increased stimulation duration from 30 s to 30 m across frequencies. Our results highlight the importance of inhibitory interneurons in modulating local circuits of the SDH and the importance of local circuit contributions to the analgesic mechanisms of SCS.