Remote Management of Spinal Cord Stimulation Devices for Chronic Pain: Expert Recommendations on Best Practices for Proper Utilization and Future Considerations.

OBJECTIVE: Emerging spinal cord stimulation (SCS) remote monitoring and programming technologies provide a unique opportunity to address challenges of in-person visits and improve patient care, although clinical guidance on implementation is needed. The goal of this document is to establish best clinical practices for integration of remote device management into the care of patients with SCS, including remote monitoring and remote programming. MATERIALS AND METHODS: A panel of experts in SCS met in July 2022, and additional experts contributed to the development of recommendations after the meeting via survey responses and correspondence. RESULTS: Major goals of remote SCS device management were identified, including prompt identification and resolution of SCS-related issues. The panel identified metrics for remote monitoring and classified them into three categories: device-related (eg, stimulation usage); measurable physiologic or disease-related (eg, patient physical activity or pedometry); and patient-reported (eg, sleep quality and pain intensity). Recommendations were made for frequency of reviewing remote monitoring metrics, although providers should tailor follow-up to individual patient needs. Such periodic reviews of remote monitoring metrics would occur separately from automatic monitoring system notifications (if key metrics fall outside an acceptable range). The guidelines were developed in consideration of reimbursement processes, privacy concerns, and the responsibilities of the care team, industry professionals, manufacturers, patients, and caregivers. Both existing and needed clinical evidence were covered, including outcomes of interest for future studies. CONCLUSIONS: Given the expansion of SCS device capabilities, this document provides critical guidance on best practices for using remote device management, although medical necessity should drive all remote monitoring decisions, with individualized patient care. The authors also describe the potential of these emerging technologies to improve outcomes for patients with SCS, although more clinical evidence is needed.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial.

OBJECTIVE: This study aimed to assess the safety and effectiveness of a new charge-distributed multiphase stimulation paradigm during an extended spinal cord stimulation (SCS) trial. MATERIALS AND METHODS: This prospective, multicenter, randomized, single-blind, feasibility study included participants with chronic low back and/or leg pain and baseline numerical rating scale (NRS) for overall pain intensity ≥6. After a successful commercial SCS trial, participants were randomized to multiphase SCS therapy A (approximately 600-1500 Hz) or B (approximately 300-600 Hz), delivered via an investigational external pulse generator and existing leads during an 11-to-12-day testing period. Primary end points were mean NRS change from baseline to final in-office visit for each multiphase therapy and between therapies. Secondary end points included mean NRS change from end of commercial trial to final study visit and incidence of device-related adverse events (AEs). Additional measures included patient-reported outcomes collected at home through electronic watches and written diaries. Power usage was compared between multiphase and commercial therapies. RESULTS: A total of 122 participants initiated a commercial trial; 77 were randomized to a multiphase arm, and 65 completed the study. Reductions in mean NRS scores from baseline to final study visit were significant for multiphase therapy A and B (-4.3 and -4.7, respectively; both p < 0.0001). There was no statistically significant difference in mean NRS reduction or percent pain relief between multiphase therapies. In an additional analysis, 63.9% of participants reported greater pain relief with multiphase than with commercial SCS therapy in the at-home setting. On average, multiphase required less power than did commercial devices. One non-serious device-related AE was reported, and no infections occurred during the extended trial. CONCLUSIONS: Multiphase SCS effectively reduced pain in participants with chronic low back and/or leg pain during a trial, with no unanticipated device-related AEs reported. Future studies should evaluate long-term effectiveness of multiphase stimulation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03594266.

Effects of Spinal Cord Stimulation in Patients with Chronic Nausea, Vomiting, and Refractory Abdominal Pain.

BACKGROUND: Patients with chronic nausea and vomiting often also have chronic abdominal pain. Spinal cord stimulation (SCS) may provide pain control, but scarce data are available regarding the effect of SCS on chronic nausea and vomiting. AIMS: We aimed to determine the effect of SCS in patients with chronic nausea, vomiting, and refractory abdominal pain. METHODS: Retrospective chart review of 26 consecutive patients who underwent SCS trial for a primary diagnosis of nausea, vomiting and refractory abdominal pain. RESULTS: 26 patients underwent SCS trial, with an average age of 48 years. Twenty-three patients (88.5%) reported > 50% pain relief during the temporary SCS trial and then underwent permanent implantation. Patients were then followed for 41 (22-62) months. At baseline, 20 of the 23 patients (87.0%) reported daily nausea, but at 6 months and the most recent follow-up, only 8 (34.8%) and 7 (30.4%) patients, respectively, had daily nausea (p < 0.001). Days of nausea decreased from 26.3 days/month at baseline to 12.8 and 11.7 days/month at 6 months and at the most recent visit, respectively. Vomiting episodes decreased by 50%. Abdominal pain scores improved from 8.7 to 3.0 and 3.2 at 6 months and the most recent visit, respectively (both p < 0.001). Opioid use decreased from 57.7 mg MSO4 equivalents to 24.3 mg at 6 months and to 28.0 mg at the latest patient visit (both p < 0.05). CONCLUSIONS: SCS may be an effective therapy for long-term treatment of symptoms for those patients afflicted with chronic nausea, vomiting, and refractory abdominal pain.

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.

Safety Analysis of Dorsal Root Ganglion Stimulation in the Treatment of Chronic Pain.

BACKGROUND: Stimulation of the dorsal root ganglion (DRG) in the treatment of chronic, intractable pain has shown excellent clinical results in multiple published studies, including a large prospective, randomized, controlled trial. Both safety and efficacy have been demonstrated utilizing this therapeutic approach for many chronic complaints. Continued assessment of neuromodulation therapies, such as DRG stimulation, are not only an important aspect of vigilant care, but are also necessary for the evaluation for safety. MATERIALS AND METHODS: Safety and complaint records for DRG and spinal cord stimulation (SCS) stimulation were obtained from the manufacturer, analyzed and compiled to further assess ongoing device safety. Complaint event data were stratified according to complain type as well as overall rates. Data from similar time periods were compared between epidural neurostimulation devices by the same manufacturer as well as rates reported in the literature. RESULTS: Overall, DRG stimulation device event rates were lower or comparable to similar epidurally placed neurostimulation devices. Rates of events varied from 0 to 1.0% for DRG stimulation (n >500+ implants) which was similar to the event rate for SCS by the same manufacturer (n >2000+ implants). In comparison, complaints and adverse events ranged from 0 to 14% for SCS in the literature. DISCUSSIONS: The current results from a large consecutive cohort obtained from manufacturer records indicates that DRG stimulation demonstrates an excellent safety profile. Reported event rates are similar to previously reported adverse event and complaint rates in the literature for this therapy. Similarly, safety events rates were lower or similar to previously reported rates for SCS, further demonstrating the comparative safety of this neuromodulation technique for chronic pain treatment.

Paresthesia-Free Dorsal Root Ganglion Stimulation: An ACCURATE Study Sub-Analysis.

INTRODUCTION: ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia. METHODS: A retrospective analysis of therapy outcomes was conducted for 61 subjects in the ACCURATE study who received a permanent DRG neurostimulator. Outcomes of subjects who were paresthesia-free were compared to those who experienced paresthesia-present therapy at 1, 3, 6, 9, and 12-month follow-ups. Predictor variables for the presence or absence of paresthesias with DRG stimulation were also explored. RESULTS: The percentage of subjects with paresthesia-free pain relief increased from 16.4% at 1-month to 38.3% at 12-months. Paresthesia-free subjects generally had similar or better outcomes for pain severity, pain interference, quality of life, and mood state as subjects with paresthesia-present stimulation. Factors that increased the odds of a subject feeling paresthesia were higher stimulation amplitudes and frequencies, number of implanted leads, and younger age. CONCLUSIONS: Some DRG subjects achieved effective paresthesia-free analgesia in the ACCURATE trial. This supports the observation that paresthesia is not synonymous with pain relief or required for optimal analgesia with DRG stimulation.

Cooled Radiofrequency Ablation Treatment of the Genicular Nerves in the Treatment of Osteoarthritic Knee Pain: 18- and 24-Month Results.

OBJECTIVE: The primary objective of this observational, prospective, multicenter study was to evaluate the long-term outcomes, including pain, function, and perceived effect of treatment, in subjects undergoing cooled radiofrequency ablation (CRFA) who have pain due to osteoarthritis (OA) of the knee. METHODS: This analysis included a subset of subjects previously enrolled in a prospective, multicenter randomized study comparing the safety and effectiveness of CRFA and intra-articular steroid injection in patients with knee OA through 12 months who were contacted to participate in this extension study. Subjects were enrolled if they agreed to participate in up to 2 additional follow-ups, at 18 and 24 months. RESULTS: Eighty-three subjects from the 5 participating sites underwent CRFA during the original study and were contacted for this extension study. Of the 33 subjects enrolled, 25 were evaluated at 18 months after CRFA treatment, and their mean numeric rating scale (NRS) score was 3.1 ± 2.7, with 12 subjects reporting ≥50% pain relief compared to baseline. At 24 months, 18 subjects reported a mean NRS score of 3.6 ± 2.8, with 11 demonstrating ≥50% pain relief. Functional improvement as measured by the Oxford Knee Score continued to be present, with an overall mean change from baseline of 26.0 ± 9.6 points at 18 months and 29.9 ± 10.4 points at 24 months. CONCLUSION: In this subset of subjects from a randomized controlled trial, CRFA provided sustained pain relief, improved function, and perceived positive effect through 24 months for subjects with OA knee pain with no safety concerns identified.

Percutaneous Peripheral Nerve Stimulation for Chronic Low Back Pain: Prospective Case Series With 1 Year of Sustained Relief Following Short-Term Implant.

INTRODUCTION: Percutaneous peripheral nerve stimulation (PNS) provides an opportunity to relieve chronic low back pain and reduce opioid analgesic consumption as an alternative to radiofrequency ablation and permanently implanted neurostimulation systems. Traditionally, the use of neurostimulation earlier in the treatment continuum has been limited by its associated risk, invasiveness, and cost. METHODS: Percutaneous PNS leads (SPRINT MicroLead) were placed bilaterally to target the medial branches of the dorsal rami nerves under image guidance. The percutaneous leads were connected to miniature wearable stimulators (SPRINT PNS System) for the 1-month therapy period, after which the leads were removed. Pain and disability were assessed long-term up to 12 months after lead removal. RESULTS: Substantial, clinically significant reductions in average pain intensity (≥50% reduction as measured by the Brief Pain Inventory Short Form) were experienced by a majority of subjects (67%) at end of treatment compared to baseline (average 80% reduction among responders; P < 0.05, analysis of variance; n = 9). Twelve months after the end of PNS treatment, a majority of subjects who completed the long-term follow-up visits experienced sustained, clinically significant reductions in pain and/or disability (67%, n = 6; average 63% reduction in pain intensity and 32-point reduction in disability among responders). No serious or unanticipated adverse events were reported. CONCLUSIONS: This study challenges the long-held notion that a positive trial of PNS should be followed by a permanent implant in responders. Percutaneous PNS may serve as an effective neurostimulation therapy for patients with chronic low back pain and should be considered earlier in the treatment continuum as a motor-sparing means of avoiding opioids, denervation, and permanently implanted neurostimulation systems.

Percutaneous Peripheral Nerve Stimulation (PNS) for the Treatment of Chronic Low Back Pain Provides Sustained Relief.

OBJECTIVES: The objective of this study was to evaluate the use of percutaneous peripheral nerve stimulation (PNS) for the treatment of chronic low back pain (LBP). Percutaneous PNS offers the potential to provide an effective neuromodulation therapy using a system and fine-wire leads designed specifically for percutaneous use with history of an excellent safety profile. MATERIALS AND METHODS: Subjects with chronic axial LBP received percutaneous PNS leads targeting the medial branch of the dorsal ramus in the region of LBP. Lead placement was guided using ultrasound and confirmed by selective activation of the lumbar multifidus and patient-reported sensations. The percutaneous fine-wire leads remained in place for the 30-day therapy. RESULTS: A majority of subjects reported statistically and clinically significant reductions in both average pain intensity (BPI-5) and worst pain intensity (BPI-3) scores with PNS treatment, which continued long term at the four-month follow-up visit. Subject-reported reductions in pain intensity were substantiated by concomitant and sustained reductions in analgesic medication usage. Subjects also reported clinically significant reductions in patient-centric outcomes of disability (Oswestry Disability Index), pain interference (BPI-9), and patient global impression of change (PGIC). CONCLUSIONS: This work demonstrates the potential value of percutaneous PNS for the treatment of chronic LBP. Improvements in pain, medication, and patient-centric outcomes, which were sustained long term after the removal of PNS leads, demonstrate the significance of this innovative approach to treat chronic LBP.

Multicenter, Randomized, Double-Blind Study Protocol Using Human Spinal Cord Recording Comparing Safety, Efficacy, and Neurophysiological Responses Between Patients Being Treated With Evoked Compound Action Potential-Controlled Closed-Loop Spinal Cord Stimulation or Open-Loop Spinal Cord Stimulation (the Evoke Study).

BACKGROUND: The spinal cord (SC) response to stimulation has yet to be studied in a pivotal clinical study. We report the study design of an ongoing multicenter, randomized, double-blind, controlled, parallel-arm study of an evoked compound action potential (ECAP) controlled closed-loop spinal cord stimulation (SCS) system, which aims to gain U.S. Food and Drug Administration approval. METHODS: This study will enroll 134 SCS candidates with chronic trunk and limb pain from up to 20 United States sites. Subjects are randomized 1:1 to receive ECAP-controlled closed-loop or open-loop, conventional SCS. The primary objective is noninferiority of closed-loop stimulation determined by the proportion of subjects with ≥50% reduction in overall trunk and limb pain and no increase in pain medications at the three-month visit. If noninferiority is met, superiority is tested. In addition, measures recommended by IMMPACT (e.g., pain intensity, functional disability, emotional functioning, quality of life, impression of change, and sleep), neurophysiological properties (e.g., SC activation, conduction velocity, chronaxie, and rheobase), and safety are analyzed. DISCUSSION: All approved SCS therapies, regardless of the presence or absence of stimulation induced paresthesias, produce fixed-output stimuli; that is, the energy delivered from the electrode array has a defined output irrespective of the neural response of SC fibers. An SCS system has been developed that directly measures the neurophysiologic activation of the SC to stimulation (i.e., ECAP amplitude) and uses this information in a feedback mechanism to produce closed-loop SCS to maintain optimal and stable activation of the SC. This study represents the first randomized, double-blind, pivotal study in the field of neuromodulation to measure SC activation in ECAP-controlled closed-loop versus open-loop stimulation and is expected to yield important information regarding differences in safety, efficacy, and neurophysiological properties. The potential clinical utility of these objective measurements of SC activation and other neurophysiological properties promises to improve outcomes of SCS for chronic pain patients.

Comparison of Paresthesia Coverage of Patient's Pain: Dorsal Root Ganglion vs. Spinal Cord Stimulation. An ACCURATE Study Sub-Analysis.

OBJECTIVES: This was a sub-analysis of the ACCURATE clinical trial that evaluated the accuracy and necessity of targeting paresthesia coverage of painful areas with dorsal root ganglion (DRG) stimulation vs. tonic spinal cord stimulation (SCS). MATERIALS AND METHODS: On diagrams of the torso and lower limbs, subjects marked where they felt pain at baseline and paresthesias at three months postimplant. Seventy-five subjects (41 DRG and 34 SCS) with diagrams of sufficient quality were scanned, digitized, and included in this analysis. Subject completed diagrams were digitized and superimposed with a grid of 1398 squares. Quantification of the percentage of bodily areas affected by pain and stimulation induced paresthesias was performed. RESULTS: The percent of painful areas covered by paresthesia was significantly lower for DRG subjects than for SCS subjects (13% vs. 28% of the painful regions, p < 0.05), possibly because significantly more DRG subjects felt no paresthesia during stimulation when compared to SCS subjects (13/41 DRG vs. 3/34 SCS) (p < 0.05). The amount of paresthesia produced outside the painful areas (unrequired paresthesia) was significantly lower in DRG subjects than that of SCS subjects. On average, the percent of unrequired paresthesia was only 20% of the subjects' total painful body surface area in the DRG group compared to 210% in the SCS group (p < 0.01). CONCLUSIONS: The results of this ACCURATE study sub-analysis show that DRG stimulation produces paresthesias, on average, that are less frequent, less intense, with a smaller footprint on the body and less dependent on positional changes.

Plasma N-glycome composition associates with chronic low back pain.

BACKGROUND: Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease. METHODS: Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery. RESULTS: We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP. CONCLUSIONS: Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation. GENERAL SIGNIFICANCE: To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology.

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).

An Integrated Quantitative Index for Measuring Chronic Multisite Pain: The Multiple Areas of Pain (MAP) Study.

OBJECTIVE: Despite the high prevalence of chronic multisite pain, there is little consensus on methods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain information with a single value. DESIGN: Single-visit, noninterventional, epidemiological study. SETTING: Fourteen outpatient multidisciplinary pain management programs. PATIENTS: Patients with chronic pain of the trunk and/or limbs for at least six months with average overall pain intensity of at least 5 on the numeric rating scale. METHODS: Development of IPQI was performed in a large population (N = 810) of chronic pain patients from the Multiple Areas of Pain (MAP) study. RESULTS: Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD = 5.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI = 0.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI values were near the middle of the scale, with mean and median IPQI at 0.52 (SD = 0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. CONCLUSIONS: IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials.

Four-Extremity Neurostimulation Using Two Cervical Octapolar Leads and High Frequency of 10 kHz.

OBJECTIVES AND METHODS: A few published reports describe successful clinical use of low-frequency spinal cord stimulation (SCS) in the cervical spine resulting in bilateral upper and lower extremity pain relief. A major side-effect when using this modality of SCS is the uneven intensity of paresthesias, which are frequently excessive in upper extremities while attempting to achieve optimal paresthesia coverage in all 4 extremities. RESULTS AND CONCLUSIONS: Here we describe a successful case of high-frequency SCS at 10 kHz where profound control of neuropathic pain of all 4 extremities was achieved without the complication of paresthesias. Discussed are future implications of such therapy.

Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Low Back Pain: Two Clinical Case Reports of Sustained Pain Relief.

As the leading cause of disability among U.S. adults, chronic low back pain (LBP) is one of the most prevalent and challenging musculoskeletal conditions. Neuromodulation provides an opportunity to reduce or eliminate the use of opioids to treat chronic LBP, but the cost and invasiveness of existing methods have limited its broad adoption, especially earlier in the treatment continuum. The present case report details the results of a novel method of short-term percutaneous peripheral nerve stimulation (PNS) in 2 subjects with chronic LBP. At the end of the 1-month therapy, stimulation was discontinued and the leads were withdrawn. PNS produced clinically significant improvements in pain (62% average reduction in Brief Pain Inventory Question #5, average pain), and functional outcomes (73% reduction in disability, Oswestry Disability Index; 83% reduction in pain interference, Brief Pain Inventory). Both subjects reduced nonopioid analgesic use by 83%, on average, and the one subject taking opioids ceased using all opioids. The only adverse event was minor skin irritation caused by a topical dressing. The clinically significant improvements were sustained at least 4 months after start of therapy (79% average reduction in pain; both reported minimal disability; 100% reduction in opioids; 74% reduction nonopioids). The results reveal the utility of this novel, short-term approach and its potential as a minimally invasive neuromodulation therapy for use earlier in the treatment continuum to produce sustained pain relief and reduce or eliminate the need for analgesic medications, including opioids, as well as more expensive and invasive surgical or therapeutic alternatives.

Twelve-Month Follow-up of a Randomized Clinical Trial Comparing Intradiscal Biacuplasty to Conventional Medical Management for Discogenic Lumbar Back Pain.

Objective: This report conveys 12-month outcomes of subjects treated with intradiscal biacuplasty (IDB) and conservative medical management (CMM) for chronic low back pain of discogenic origin, and results for subjects who elected to receive IDB + CMM 6 months after CMM-alone. Methods: Sixty-three subjects were originally randomized to the IDB + CMM group (N = 29) or CMM-alone (N = 34). Six months following continuous CMM-alone treatment, participants in this study group were permitted to "cross-over" to IDB + CMM (N = 25), and followed for an additional 6 months. The original IDB + CMM study subjects were followed for a total of 12 months (N = 22). Results: Pain reduction at 12 months was statistically significant and clinically meaningful in the original IDB + CMM group compared to baseline. Functional and disability outcomes were also improved statistically and clinically. Fifty-five percent of the IDB + CMM patients responded to treatment with a mean VAS reduction of 2.2 points at 12 months. Furthermore, 50% and 64% of subjects reported clinically significant improvements in SF36-PF and in ODI, respectively. There was a 1.7-point reduction (improvement) on a 7-point PGIC scale, and a 0.13-point increase (improvement) in the EQ-5D Health Index. Fifty-percent of cross-over subjects responded to IDB + CMM intervention. Mean outcome scores for cross-over subjects were similar to those of the originally-treated subjects, and functional and disability endpoints were improved statistically and clinically compared to respective baseline values. Conclusions: The study demonstrated long-term clinical effectiveness of IDB + CMM for treating chronic lumbar discogenic pain. Furthermore, the cross-over study subjects experienced similar improvements in pain, function, disability, and satisfaction.

Prospective, Multicenter, Randomized, Double-Blinded, Partial Crossover Study to Assess the Safety and Efficacy of the Novel Neuromodulation System in the Treatment of Patients With Chronic Pain of Peripheral Nerve Origin.

INTRODUCTION: Currently available central nervous system treatment strategies are often insufficient in management of peripheral neuropathic pain, prompting a resurgence of neuromodulation focused on peripheral pain. A new peripheral nerve stimulation device was investigated in a prospective, randomized, double blind, crossover study, looking specifically at efficacy and safety, with Food and Drug Administration oversight. METHODS: Prospective, multicenter, randomized, double-blind, partial crossover study to assess safety and efficacy. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance. RESULTS: One hundred forty-seven patients were consented and screened for the study. Thirty-five did not meet inclusion or exclusion criteria. Ninety-four patients were implanted and then randomized to the treatment (45) or the Control group (49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the Treatment group had significantly better improvement than the Control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting. CONCLUSION: The novel peripheral nerve stimulation device is a safe and effective treatment strategy to address neuropathic pain of peripheral nerve origin.

Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial.

BACKGROUND: Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain. METHODS: A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit. RESULTS: At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P < 0.001). HF10 therapy subjects did not experience paresthesias. CONCLUSION: HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.