A Prospective, Multi-Center, Clinical Trial of a 10-kHz Spinal Cord Stimulation System in the Treatment of Chronic Pelvic Pain.

BACKGROUND: Chronic pelvic pain (CPP) is a debilitating condition that often leads to disability and does not respond to conventional treatments. This study was conducted to evaluate the effects of paresthesia-independent 10-kHz spinal cord stimulation (SCS) in subjects with CPP. METHODS: This prospective, single-arm pilot study enrolled subjects with clinical diagnoses of CPP and mean pain scores of ≥ 5.0 cm on a 10-cm VAS. Subjects underwent trial stimulations with 10-kHz SCS, and those who had successful trial stimulations (≥40% pain relief) received permanently implanted devices and were followed for 12 months. RESULTS: Of the 21 subjects who underwent the 10-kHz SCS trial, 17 were successful and 14 subjects received permanent implants. No neurological deficits were observed in any subjects and all adverse events (AEs) were resolved without sequelae during the study period. Over 12 months, mean VAS scores decreased by 72% from baseline, and 10 of 13 subjects (77%) were responders (≥50% pain relief). Pain remission (VAS score ≤ 3.0 cm) was reported by 8 of 13 subjects (62%), and mean pain scores on the short-form McGill Pain Questionnaire 2 decreased as well. Pain Disability Index scores declined by 29 points, and 85% of the subjects reported satisfaction. CONCLUSIONS: Paresthesia-independent stimulation with 10-kHz SCS reduced pelvic pain in subjects with CPP and was not associated with any unexpected AEs. While larger, controlled studies are needed, results of this study suggest that this therapeutic modality could potentially treat patients with CPP while improving their quality of life.

Ten kHz spinal cord stimulation for the treatment of chronic peripheral polyneuropathy: 12-Month results from prospective open-label pilot study.

BACKGROUND: The goal of this study was to demonstrate that the paresthesia-independent 10 kHz spinal cord stimulation (SCS) can provide long-term pain relief in patients with peripheral polyneuropathy (PPN). Clinically diagnosed subjects with PPN refractory to conventional medical management were enrolled in this prospective, multicenter study between November 2015 and August 2016, after institutional review board approval and patient informed consent were obtained. METHODS: Subjects underwent trial stimulation utilizing 2 epidural leads, and if successful, were implanted with a permanent 10 kHz SCS system and followed up for 12 months post-implant. Outcome measures included adverse events, pain, neurological assessments, disability, function, quality of life, pain interference, sleep, satisfaction, and global impression of change. Data are presented as descriptive statistics. Permanent implant population results are reported as mean ± standard error. RESULTS: Twenty-one of the 26 trialed subjects had a successful trial and 18 received a permanent implant. All subjects had the leads placed anatomically without the need for paresthesia. Subjects experienced significant and sustained pain relief (at least 65% at all timepoints) whereas physicians noted improvements in neurological function. Significant improvements in disability, function, sleep, sensory, and affective dimensions of pain were reported at all timepoints. All adverse events were resolved without sequelae. CONCLUSION: Findings from this study suggest that 10 kHz SCS may provide sustained pain relief and disability improvements in patients suffering from PPN.

High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Nonsurgical Refractory Back Pain: Design of a Pragmatic, Multicenter, Randomized Controlled Trial.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to provide pain relief for chronic back and leg pain due to failed back surgery syndrome. But many patients with chronic back pain have not had major back surgery or are not good candidates for surgery, and conventional medical management (CMM) provides limited relief. We have termed this condition nonsurgical refractory back pain (NSRBP). Level 1 evidence does not yet exist showing the therapeutic benefit of SCS for NSRBP. OBJECTIVE: To compare 10-kHz SCS plus CMM (10-kHz SCS + CMM) to CMM alone for treatment of NSRBP in terms of clinical and cost effectiveness. STUDY DESIGN: Multicenter, randomized controlled trial (RCT), with subjects randomized 1:1 to either 10-kHz SCS + CMM or CMM alone. Optional crossover occurs at 6 months if treatment does not achieve ≥50% pain relief. METHODS: Patients with NSRBP as defined above may be enrolled if they are ineligible for surgery based on surgical consultation. Subjects randomized to 10-kHz SCS + CMM will receive a permanent implant if sufficient pain relief is achieved in a temporary trial. Both groups will receive CMM per standard of care and will undergo assessments at baseline and at follow-ups to 12 months. Self-report outcomes include pain, disability, sleep, mental health, satisfaction, healthcare utilization, and quality of life. RESULTS: Enrollment was initiated on September 10, 2018. Prespecified independent interim analysis at 40% of the enrollment target indicated the sample size was sufficient to show superiority of treatment at the primary endpoint; therefore, enrollment was stopped at 211. CONCLUSIONS: This large multicenter RCT will provide valuable evidence to guide clinical decisions in NSRBP.

10 kHz Spinal Cord Stimulation for the Treatment of Failed Back Surgery Syndrome with Predominant Leg Pain: Results from a Prospective Study in Patients from the Dutch Healthcare System.

INTRODUCTION: Persistent back/and or leg pain is a common outcome after spinal surgery (otherwise known as failed back surgery syndrome [FBSS]). Studies have shown that spinal cord stimulation (SCS) at 10 kHz provides effective analgesia in FBSS patients with both back and leg pain symptoms and in those with predominant back pain. This study is the first to evaluate the therapy in FBSS patients with predominant leg pain. METHODS: The safety and efficacy of 10 kHz SCS was evaluated in an uncontrolled, open-label, prospective study of FBSS patients with predominant leg pain in the Netherlands. Follow-ups were performed at 1, 3, 6, and 12 months post implantation. RESULTS: Sixty out of 68 patients (88%) experienced sufficient pain relief during a stimulation trial. Of these, 58 proceeded to permanent implantation of a 10 kHz SCS system. After 12 months of treatment, 80% of patients experienced ≥ 50% reduction in baseline leg pain, and a similar proportion (76%) experienced ≥ 50% reduction in baseline back pain. At least two-thirds of patients were also leg pain and back pain remitters (visual analog scale [VAS] ≤ 2.5 cm). The therapy was also associated with a general improvement in patients' quality of life, as measured by secondary outcomes including disability, perception of health improvement, mental well-being, and satisfaction. A positive impact on opioid consumption was also observed. CONCLUSIONS: Consistent with previous findings, 10 kHz SCS for the treatment of FBSS patients with predominant radicular symptoms is safe and effective and is associated with improved quality of life.

10-kHz Spinal Cord Stimulation for Chronic Postsurgical Pain: Results From a 12-Month Prospective, Multicenter Study.

BACKGROUND: Chronic postsurgical pain (CPSP) can be caused by peripheral nerve injury (PNI) resulting from surgical procedures and has a significant neuropathic component. This prospective, single-arm study was conducted to document the effectiveness of 10-kHz spinal cord stimulation (10-kHz SCS) as a treatment for patients with CPSP. METHODS: Subjects with CPSP who were refractory to conventional medical interventions and reported pain scores of ≥5 cm on a 10-cm VAS underwent trial stimulations lasting up to 14 days. Epidural leads were implanted at locations appropriate for the primary area of pain, and trials resulting in ≥40% pain relief were considered successful. Subjects with successful trials underwent implantation with a permanent 10-kHz SCS system and were followed for 12 months after implantation. RESULTS: Of the 34 subjects who underwent trial stimulation, 1 was withdrawn early and 29 (87.9%) had a successful trial and received a permanent implant. After 12 months of treatment, the mean VAS score decreased by 6.5 cm, the response rate was 88.0% (22/25), and 18 subjects (62.1%) were remitters with VAS scores sustained at ≤3.0 cm. Scores for all components of the short-form McGill Pain Questionnaire 2 were significantly reduced, including affective descriptors of pain. Pain catastrophizing and vigilance, patient function, physical and mental well-being, and sleep quality all improved over the course of the study. No neurologic deficits reported in the study. CONCLUSIONS: 10-kHz SCS is effective and tolerated in patients with CPSP, and further study of its clinical application in this population is warranted.

Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT.

PURPOSE: Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual's life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. METHODS: A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. RESULTS: At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a "moderate" or "minimal" impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. CONCLUSIONS: In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01609972).

Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP).

OBJECTIVES: Phantom limb pain (PLP) is a neuropathic condition in which pain is perceived as arising from an amputated limb. PLP is distinct from, although associated with, pain in the residual limb and nonpainful phantom sensations of the missing limb. Its treatment is extremely challenging; pharmaceutical options, while commonly employed, may be insufficient or intolerable. Neuromodulatory interventions such as spinal cord stimulation have generated mixed results and may be limited by poor somatotopic specificity. It was theorized that dorsal root ganglion (DRG) neuromodulation may be more effective. MATERIALS AND METHODS: Patients trialed a DRG neurostimulation system for their PLP and were subsequently implanted if results were positive. Retrospective chart review was completed, including pain ratings on a 100-mm visual analogue scale (VAS) and patient-reported outcomes. RESULTS: Across eight patients, the average baseline pain rating was 85.5 mm. At follow-up (mean of 14.4 months), pain was rated at 43.5 mm. Subjective ratings of quality of life and functional capacity improved. Some patients reduced or eliminated pain medications. Patients reported precise concordance of the paresthesia with painful regions, including in their phantom limbs; in one case, stimulation eliminated PLP as well as nonpainful phantom sensations. Three patients experienced a diminution of pain relief, despite good initial outcomes. CONCLUSIONS: DRG neuromodulation may be an effective tool in treating this pain etiology. Clinical outcomes in this report support recent converging evidence suggesting that the DRG may be the site of PLP generation and/or maintenance. Further research is warranted to elucidate mechanisms and optimal treatment pathways.

Inhibition of bladder overactivity by stimulation of feline pudendal nerve using transdermal amplitude-modulated signal (TAMS).

OBJECTIVE: • To develop a non-invasive neuromodulation method targeting the pudendal nerve. MATERIALS AND METHODS: • Bladder overactivity induced by acetic acid (AA) irritation was partially suppressed by electrical stimulation of the pudendal nerve in α-chloralose anaesthetized cats using a transdermal amplitude-modulated signal (TAMS). RESULTS: • During cystometrography (CMG), intravesical infusion of 0.25% AA significantly decreased the mean (se) bladder capacity to 28.8 (5.9)% of the capacity measured during saline infusion. • The TAMS stimulation inhibited AA-induced bladder overactivity at 5, 7 and 10 Hz, and significantly increased the mean (se) bladder capacity to 61.8 (9.9)%, 51.3 (14.5)%, 53.6 (14.9)%, respectively, of the control capacity during saline infusion, whereas stimulation at 20-40 Hz had no effect. • Under isovolumetric conditions at a bladder volume ranging between 130 to 160% of the bladder capacity measured during AA infusion, TAMS stimulation at all frequencies (5-40 Hz) significantly suppressed the irritation-induced rhythmic bladder contractions, reduced the area under the bladder pressure curve, and decreased the frequency of bladder contractions. However, the amplitude of rhythmic bladder contractions was only significantly decreased at stimulation frequencies of 5-20 Hz. • At bladder volumes above the AA control capacity, TAMS stimulation with frequencies of 20-30 Hz had an excitatory effect, resulting in large amplitude (>25 cmH(2) O) bladder contractions. CONCLUSIONS: • TAMS stimulation targeting the cat pudendal nerve can inhibit C-fibre afferent-mediated bladder overactivity. • Thus, clinical research seems warranted to explore the usefulness of this technology for patients with overactive bladder symptoms.

Bladder inhibition by intermittent pudendal nerve stimulation in cat using transdermal amplitude-modulated signal (TAMS).

AIMS: To determine if intermittent stimulation of the pudendal nerve using a transcutaneous stimulation method can inhibit reflex bladder activity. Intermittent stimulation consumes less electrical power than continuous stimulation, requiring a smaller battery and reducing the size of the stimulator for neuromodulation therapy. METHODS: A non-invasive stimulation method employing a transdermal amplitude-modulated signal (TAMS) was used in 18 α-chloralose anesthetized cats to stimulate the pudendal nerve via electrodes attached to the skin surface. Intermittent stimulation of different duty cycles was applied during repeated cystometrograms (CMGs) to inhibit reflex bladder activity. The bladder capacity measured during each CMG was used to indicate the inhibitory effect induced by the stimulation. RESULTS: Continuous stimulation maximally increased bladder capacity to 172.6 ± 15% of the control capacity, while intermittent stimulation at the duty cycles of 30/30, 5/5, and 1/1 ("on/off" in seconds) significantly (P < 0.05) increased bladder capacity to 132 ± 7.5%, 154.2 ± 20%, and 165.5 ± 28%, respectively. The inhibitory effect was gradually reduced as the "on/off" ratio was decreased. CONCLUSIONS: This pre-clinical study indicated that intermittent stimulation of the pudendal nerve could be as effective as continuous stimulation to inhibit reflex bladder activity. These results are useful for the design and development of new stimulator technology to treat overactive bladder, and are also important for understanding pudendal neuromodulation therapy.

A systematic review of clinical studies of electrical stimulation for treatment of lower urinary tract dysfunction.

INTRODUCTION AND HYPOTHESIS: The aim of this manuscript was to provide a systematic literature review of clinical trial evidence for a range of electrical stimulation therapies in the treatment of lower urinary tract symptoms (LUTS). METHODS: The databases MEDLINE, BIOSIS Previews, Inside Conferences, and EMBASE were searched. Original clinical studies with greater than 15 subjects were included. RESULTS: Seventy-three studies were included, representing implanted sacral nerve stimulation (SNS), percutaneous posterior tibial nerve stimulation (PTNS), and transcutaneous electrical stimulation (TENS) therapy modalities. CONCLUSIONS: Median mean reductions in incontinence episodes and voiding frequency were similar for implanted SNS and PTNS. However, long-term follow-up data to validate the sustained benefit of PTNS are lacking. Despite a substantial body of research devoted to SNS validation, it is not possible to definitively define the appropriate role of this therapy owing largely to study design flaws that inhibited rigorous intention to treat analyses for the majority of these studies.

Neuromodulation of bladder activity by stimulation of feline pudendal nerve using a transdermal amplitude modulated signal (TAMS).

AIM: To develop a non-invasive neuromodulation method to regulate bladder activity. METHODS: Neuromodulation of bladder activity was investigated in felines with an intact spinal cord under α-chloralose anesthesia using a transcutaneous stimulation method with surface electrodes attached to the skin area between the base of the tail and the sciatic notch. RESULTS: The bladder could be either inhibited or excited depending on stimulation frequency and bladder volume. With the bladder distended to induce large amplitude rhythmic isovolumetric bladder contractions, stimulation at a frequency between 5 and 7 Hz significantly suppressed the contractions. Stimulation applied during a cystometrogram (CMG) also increased bladder capacity by 44.3 ± 10.8%. At a frequency between 20 and 40 Hz the inhibitory effect on rhythmic bladder contractions was weak and did not increase bladder capacity during CMG. At low bladder volumes ranging between 60% and 100% of the bladder capacity 20 Hz stimulation-induced small amplitude (21.2 ± 14.6 cmH(2) O) bladder contractions. However, stimulation at 20 Hz induced large amplitude (111.7 ± 22.2 cmH(2) O) bladder contractions at a bladder volume about 100-110% of the bladder capacity after the rhythmic bladder contractions were completely inhibited by the inhibitory 5 Hz stimulation. CONCLUSIONS: Both inhibitory and excitatory effects on bladder activity can be obtained in cats using the non-invasive neural stimulation approach. This pre-clinical study warrants a further clinical trial to investigate the possibility of using this non-invasive stimulation method to treat incontinence or urinary retention.

Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. Interventions: Implanted medical device delivering 10-kHz SCS. Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. Trial Registration: ClincalTrials.gov Identifier: NCT03228420.

10-kHz spinal cord stimulation treatment for painful diabetic neuropathy: results from post-hoc analysis of the SENZA-PPN study.

Aim: Previous studies of 10 kHz spinal cord stimulation demonstrated its safety and efficacy for treatment of neuropathic pain of the trunk and/or limbs. This study analyzed data from a subset of subjects with painful diabetic neuropathy enrolled in a prospective, multicenter study of peripheral polyneuropathy with various etiologies. Materials & methods: Of the eight subjects that had permanent devices, seven attended the 12-month follow-up assessment. Results & conclusion: At 12 months, 6/7 subjects were treatment responders (≥50% pain relief) and had pain remission (visual analog scale ≤ 3.0 cm). Worsening of neurologic deficits was not reported in any subject. Instead, 5/7 subjects showed improvements in sensory testing and/or reflexes. These results support further investigation of 10 kHz spinal cord stimulation as a safe and effective treatment for intractable painful diabetic neuropathy.

Opioid-sparing effects of 10 kHz spinal cord stimulation: a review of clinical evidence.

Chronic pain is a common condition that affects the physical, emotional, and mental well-being of patients and can significantly diminish their quality of life. Due to growing concerns about the substantial risks of long-term opioid use, both governmental agencies and professional societies have recommended prioritizing the use of nonpharmacologic treatments, when suitable, in order to reduce or eliminate the need for opioid use. The use of 10 kHz spinal cord stimulation (10 kHz SCS) is one such nonpharmacologic alternative for the treatment of chronic, intractable pain of the trunk and limbs. This review examines published clinical data regarding the efficacy of 10 kHz SCS for decreasing chronic pain in patients and its potential to reduce or eliminate opioid usage. Multiple prospective and retrospective studies in patients with intractable pain demonstrated that 10 kHz SCS treatment provided ≥50% pain relief in >70% patients after at least 1 year of treatment. Pain relief with 10 kHz SCS therapy ranged from 54% to 87% in the studies. More importantly, the mean daily dose of opioids required by patients in these studies was reduced after 10 kHz SCS treatment, and on average over 60% patients in studies either reduced or eliminated opioids at the last follow-up.

High-Frequency Spinal Cord Stimulation at 10 kHz for the Treatment of Combined Neck and Arm Pain: Results From a Prospective Multicenter Study.

BACKGROUND: Intractable neck and upper limb pain has historically been challenging to treat with conventional spinal cord stimulation (SCS) being limited by obtaining effective paresthesia coverage. OBJECTIVE: To assess the safety and effectiveness of the 10-kHz SCS system, a paresthesia-independent therapy, in the treatment of neck and upper limb pain. METHODS: Subjects with chronic, intractable neck and/or upper limb pain of ≥5 cm (on a 0-10 cm visual analog scale [VAS]) were enrolled in 6 US centers following an investigational device exemption from the Food and Drug Administration (FDA) and institutional review board approval. Each subject was implanted with 2 epidural leads spanning C2-C6 vertebral bodies. Subjects with successful trial stimulation were implanted with a Senza® system (Nevro Corp) and included in the evaluation of the primary safety and effectiveness endpoints. RESULTS: In the per protocol population, the primary endpoint (≥50% pain relief at 3 mo) was achieved in 86.7% (n = 39/45) subjects. Compared to baseline, subjects reported a significant reduction (P < .001) in their mean (± standard error of the mean) VAS scores at 12-mo assessment for neck pain (7.6 ± 0.2 cm, n = 42 vs 1.5 ± 0.3 cm, n = 37) and upper limb pain (7.1 ± 0.3 cm, n = 24 vs 1.0 ± 0.2 cm, n = 20). At 12-mo assessment, 89.2% of subjects with neck pain and 95.0% with upper limb pain had ≥50% pain relief from baseline, 95.0% reported to be "satisfied/very satisfied" and 30.0% either eliminated or reduced their opioid intake. CONCLUSION: In conclusion, 10-kHz SCS can treat intractable neck and upper limb pain with stable long-term outcomes.

Ten kilohertz SCS for Treatment of Chronic Upper Extremity Pain (UEP): Results from Prospective Observational Study.

BACKGROUND: Chronic upper extremity pain (UEP) has complex etiologies and is often disabling. It has been shown that 10 kHz SCS can provide paresthesia-free and durable pain relief in multiple pain types and improve the quality of life of patients. OBJECTIVE: To gain additional evidence on the safety and effectiveness of 10 kHz SCS for the treatment of chronic UEP. STUDY DESIGN: It was a prospective, multicenter, and observational study. The study was registered on ClinicalTrials.gov prospectively (clinical trial identifier: NCT02703818). SETTING: Multicenter. PATIENTS INTERVENTION AND MAIN OUTCOMES: A total of 43 subjects with chronic UEP of ≥5 cm (on a 0-10 cm visual analog scale; VAS) underwent a trial of 10 kHz SCS, and subjects with ≥40% pain relief received a permanent implant. All subjects had upper limb pain at baseline, while some had concomitant shoulder or neck pain. Subject outcomes were assessed for 12 months, and the primary outcome was the responder rate (percentage of subjects experiencing ≥50% pain relief from baseline) at three months. RESULTS: Thirty-eight subjects successfully completed the trial (88.3% success rate), 33 received permanent implants (five withdrew consent), and 32 had device activation (per protocol population). There were no paresthesias or uncomfortable changes in stimulation related to changes in posture during the study and there were no neurological deficits. Responder rates at 12 months for upper limb, shoulder, and neck pain in per protocol population (N=32) were 78.1%, 85.2%, and 75.0%, respectively. At 12 months, 84.4% of subjects were satisfied or very satisfied with 10 kHz SCS, and 38.7% either reduced or eliminated opioid usage. CONCLUSION: This study further supports the effectiveness of 10 kHz SCS for chronic UEP treatment and documents the safety profile of the therapy. CLINICAL TRIAL IDENTIFIER: NCT02703818.

Treatment of Chronic Abdominal Pain With 10-kHz Spinal Cord Stimulation: Safety and Efficacy Results From a 12-Month Prospective, Multicenter, Feasibility Study.

INTRODUCTION: Chronic abdominal pain (CAP) can arise from multiple conditions, including inflammatory disorders, trauma because of injury or surgery, or structural or functional causes. This prospective, single-arm study was designed to evaluate the safety and efficacy of 10-kHz spinal cord stimulation (SCS) in patients with intractable CAP over a 12-month follow-up period. METHODS: Subjects with CAP who had been refractory to conventional medical treatment for at least 3 months resulting in self-reported pain scores of ≥5 cm on a 10-cm visual analog scale were enrolled at 4 centers in the United States. Study subjects underwent a trial stimulation lasting up to 14 days with epidural leads implanted from the vertebral levels T4 through T8. Subjects who had ≥40% pain relief during the trial stimulation period were implanted with a Senza system (Nevro Corp., Redwood City, CA) and followed up to 12 months after surgery. RESULTS: Twenty-three of 24 subjects (95.8%) had a successful trial stimulation and proceeded to a permanent implant. After 12 months of treatment with 10-kHz SCS, 78.3% of subjects were responders (pain relief of ≥50%) and 14 of 22 subjects (63.6%) were remitters (sustained ≤3.0-cm visual analog scale scores). Secondary outcomes, including assessments of disability, mental and physical well-being, sleep quality, perception of improvement, and satisfaction, showed that 10-kHz SCS greatly improved the quality of life of patients with CAP. Observationally, most subjects also reported concurrent reduction or resolution of nausea and/or vomiting. DISCUSSION: 10-kHz SCS can provide durable pain relief and improve the quality of life in patients with CAP.

High-frequency spinal cord stimulation at 10 kHz for the treatment of painful diabetic neuropathy: design of a multicenter, randomized controlled trial (SENZA-PDN).

BACKGROUND: Painful diabetic neuropathy (PDN), a debilitating and progressive chronic pain condition that significantly impacts quality of life, is one of the common complications seen with long-standing diabetes mellitus. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) has provided significant and long-term pain relief for patients with PDN. This study aims to document the value of 10-kHz SCS in addition to conventional medical management (CMM) compared with CMM alone in patients with refractory PDN. METHODS: In a prospective, multicenter, randomized controlled trial (SENZA-PDN), 216 subjects with PDN will be assigned 1:1 to receive 10-kHz SCS combined with CMM or CMM alone after appropriate institutional review board approvals and followed for 24 months. Key inclusion criteria include (1) symptoms of PDN for at least 12 months, (2) average pain intensity of at least 5 cm-on a 0- to 10-cm visual analog scale (VAS)-in the lower limbs, and (3) an appropriate candidate for SCS. Key exclusion criteria include (1) large or gangrenous ulcers or (2) average pain intensity of at least 3 cm on VAS in the upper limbs or both. Along with pain VAS, neurological assessments, health-related quality of life, sleep quality, and patient satisfaction will be captured. The primary endpoint comparing responder rates (≥50% pain relief) and safety rates between the treatment groups will be assessed at 3 months. Several secondary endpoints will also be reported on. DISCUSSION: Enrollment commenced in 2017 and was completed in 2019. This study will help to determine whether 10-kHz SCS improves clinical outcomes and health-related quality of life and is a cost-effective treatment for PDN that is refractory to CMM. TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT03228420 (registered 24 July 2017).

10 kHz SCS therapy for chronic pain, effects on opioid usage: Post hoc analysis of data from two prospective studies.

Chronic pain, including chronic low back and leg pain are prominent causes of disability worldwide. While patient management aims to reduce pain and improve daily function, prescription of opioids remains widespread despite significant adverse effects. This study pooled data from two large prospective trials on 10 kHz spinal cord stimulation (10 kHz SCS) in subjects with chronic low back pain and/or leg pain and performed post hoc analysis on changes in opioid dosage 12 months post 10 kHz SCS treatment. Patient-reported back and leg pain using the visual analog scale (VAS) and opioid dose (milligrams morphine equivalent/day, MME/day) were compared at 12 months post-10 kHz SCS therapy to baseline. Results showed that in the combined dataset, 39.3% of subjects were taking >90 MME dose of opioids at baseline compared to 23.0% at 12 months post-10 kHz SCS therapy (p = 0.007). The average dose of opioids in >90 MME group was significantly reduced by 46% following 10 kHz SCS therapy (p < 0.001), which was paralleled by significant pain relief (P < 0.001). In conclusion, current analysis demonstrates the benefits of 10 kHz SCS therapy and offers an evidence-based, non-pharmaceutical alternative to opioid therapy and/or an adjunctive therapy to facilitate opioid dose reduction whilst delivering significant pain relief. Healthcare providers involved in management of chronic non-cancer pain can include reduction or elimination of opioid use as part of treatment plan when contemplating 10 kHz SCS.

A multicenter real-world review of 10 kHz SCS outcomes for treatment of chronic trunk and/or limb pain.

Objectives: High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be efficacious in the treatment of chronic back and leg pain in a randomized, controlled, trial (SENZA-RCT). However, large observational studies have yet to be published. Therefore, we performed a real-world, multicenter, retrospective, review of therapy efficacy in 1660 patients with chronic trunk and/or limb pain. Methods: Data were collected in a real-world environment and retrospectively sourced from a global database. Included patients were trialed and/or permanently implanted with HF-SCS at 10 kHz between April 2014 and January 2018. We evaluated responder rates at 3, 6, and 12 months post-implantation. Response was defined as ≥50% pain relief from baseline. A last visit analysis included responder rate along with overall change in function, sleep, quality of life, and medication intake versus baseline. Results: Eighty-four percent of our HF-SCS-treated patients had both chronic back and leg pain. At least 70% of patients reported response to therapy throughout 12 months of follow-up. This sustained responder rate was corroborated by the last visit value (74.1%). Most patients reported concomitant improvements in function (72.3%), sleep (68.0%), and quality of life (90.3%) at their last visit versus baseline. Thirty-two percent of patients reported decreased medication intake at their last visit. Interpretation: Sustained and effective pain relief was experienced by >70% of our HF-SCS-treated patients, consistent with the findings of a previously published randomized, controlled, trial. Our review provides complementary evidence to support the treatment of chronic back and leg pain with this therapy.