Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

Safety and Efficacy of 10 kHz Spinal Cord Stimulation for the Treatment of Refractory Chronic Migraine: A Prospective Long-Term Open-Label Study.

BACKGROUND: Refractory chronic migraine (rCM) is a highly disabling condition for which novel safe and effective treatments are needed. Safety and long-term efficacy of paresthesia-free high cervical 10 kHz spinal cord stimulation (SCS) were here prospectively evaluated for the treatment of rCM. MATERIALS AND METHODS: Twenty adults with rCM (mean numbers of preventive treatments failed: 12.2 ± 3.1) were enrolled in this single-center, open-label, prospective study and implanted with a 10 kHz SCS system (Senza™ system, Nevro Corp), with the distal tip of the lead(s) positioned epidurally at the C2 vertebral level. Safety and effectiveness outcomes, such as adverse events, headache and migraine reductions, responder rates, Migraine Disability Assessment (MIDAS), Headache Impact Test-6 (HIT-6), and Migraine-Specific Quality-of-Life (MSQ), were captured up to 52 weeks after implantation. RESULTS: Compared to baseline, at 52 weeks postimplantation, there was a significant reduction of mean monthly migraine days (MMD) by 9.3 days (p < 0.001). Sixty percent and 50% of patients obtained respectively at least 30% and at least 50% reduction in mean MMD. By week 52, 50% of patients' chronic pattern converted to an episodic pattern. The proportion of subjects classified with severe headache-related disability on the HIT-6, decreased from 100% to 60% at week 52. Meaningful improvements of headache-related quality of life measured by the MSQ scale were observed with mean gain of 24.9 ± 23.1 (p < 0.001) points at 52 weeks. No unanticipated adverse device effects occurred. No patients required any additional device surgical revision. CONCLUSION: 10 kHz SCS may a be safe and effective neurostimulation option for rCM patients. The paresthesia-free waveform constitutes an unprecedented advantage for future methodologically sound sham-controlled studies in headache neuromodulation.

Comparison of Paresthesia Mapping With Anatomic Placement in Burst Spinal Cord Stimulation: Long-Term Results of the Prospective, Multicenter, Randomized, Double-Blind, Crossover CRISP Study.

OBJECTIVES: Spinal cord stimulation (SCS) is an effective therapy for chronic intractable pain. Conventional SCS involves electrode placement based on intraoperative paresthesia mapping; however, newer paradigms like burst may allow for anatomic placement of leads. Here, for the first time, we report the one-year safety and efficacy of burst SCS delivered using a lead placed with conventional, paresthesia mapping, or anatomic placement approach in subjects with chronic low back pain (CLBP). MATERIALS AND METHODS: Subjects with CLBP were implanted with two leads. The first lead was placed to cross the T8/T9 disc and active contacts for this lead were chosen through paresthesia mapping. The second lead was placed at the T9/T10 spinal anatomic landmark. Subjects initially underwent a four-week, double-blinded, crossover trial with a two-week testing period with burst SCS delivered through each lead in a random order. At the end of trial period, subjects expressed their preference for one of the two leads. Subsequently, subjects received burst SCS with the preferred lead and were followed up at 3, 6, and 12 months. Pain intensity (visual analog scale), quality-of-life (EuroQol-5D instrument), and disability (Oswestry Disability Index) were evaluated at baseline and follow-up. RESULTS: Forty-three subjects successfully completed the trial. Twenty-one preferred the paresthesia mapping lead and 21 preferred the anatomic placement lead. Anatomic placement lead was activated in one subject who had no preference. The pain scores (for back and leg) significantly improved from baseline for both lead placement groups at all follow-up time points, with no significant between-group differences. CONCLUSIONS: This study demonstrated that equivalent clinical benefits could be achieved with burst SCS using either paresthesia mapping or anatomic landmark-based approaches for lead placement. Nonparesthesia-based approaches, such as anatomic landmark-based lead placement investigated here, have the potential to simplify implantation of SCS and improve current surgical practice.

The Effect of Spinal Cord Stimulation Frequency on the Neural Response and Perceived Sensation in Patients With Chronic Pain.

BACKGROUND: The effect of spinal cord stimulation (SCS) amplitude on the activation of dorsal column fibres has been widely studied through the recording of Evoked Compound Action Potentials (ECAPs), the sum of all action potentials elicited by an electrical stimulus applied to the fibres. ECAP amplitude grows linearly with stimulus current after a threshold, and a larger ECAP results in a stronger stimulus sensation for patients. This study investigates the effect of stimulus frequency on both the ECAP amplitude as well as the perceived stimulus sensation in patients undergoing SCS therapy for chronic back and/or leg pain. METHODS: Patients suffering with chronic neuropathic lower-back and/or lower-limb pain undergoing an epidural SCS trial were recruited. Patients were implanted according to standard practice, having two 8-contact leads (8 mm inter-electrode spacing) which overlapped 2-4 contacts around the T9/T10 interspace. Both lead together thus spanning about three vertebral levels. Neurophysiological recordings were taken during the patient's trial phase at two routine follow-ups using a custom external stimulator capable of recording ECAPs in real-time from all non-stimulating contacts. Stimulation was performed at various vertebral levels, varying the frequency (ranging from 2 to 455 Hz) while all other stimulating variables were kept constant. During the experiments subjects were asked to rate the stimulation-induced sensation (paraesthesia) on a scale from 0 to 10. RESULTS: Frequency response curves showed an inverse relationship between stimulation sensation strength and ECAP amplitude, with higher frequencies generating smaller ECAPs but stronger stimulation-induced paraesthesia (at constant stimulation amplitude). Both relationships followed logarithmic trends against stimulus frequency meaning that the effects on ECAP amplitude and sensation are larger for smaller frequencies. CONCLUSION: This work supports the hypothesis that SCS-induced paraesthesia is conveyed through both frequency coding and population coding, fitting known psychophysics of tactile sensory information processing. The inverse relationship between ECAP amplitude and sensation for increasing frequencies at fixed stimulus amplitude questions common assumptions of monotonic relationships between ECAP amplitude and sensation strength.

Multicentre, clinical trial of burst spinal cord stimulation for neck and upper limb pain NU-BURST: a trial protocol.

BACKGROUND: Spinal cord stimulation (SCS) is an established therapy for chronic neuropathic pain and most frequently utilised for Failed Back Surgery Syndrome (FBSS). BurstDR™ also known as DeRidder Burst-SCS, a novel waveform, has demonstrated superiority to conventional tonic stimulation of the thoracic spine in FBSS. There are case reports of an improvement in multidimensional pain outcomes using DeRidder Burst-SCS in the cervical spine for chronic neck and cervical radicular pain. The safety and efficacy of cervical DeRidder Burst-SCS stimulation still however remain undetermined. METHODS/DESIGN: This is a prospective, multicentre feasibility trial evaluating the safety and therapeutic efficacy of DeRidder Burst-SCS stimulation for the treatment of chronic intractable neck pain with or without radiation to the arm, shoulder, and upper back. After baseline evaluation, subjects will undergo an SCS trial using the Abbott Invisible Trial system according to standard clinical procedures. During the trial phase, SCS leads will be implanted in the cervical epidural space. At the end of the SCS trial, subjects experiencing at least 50% pain relief will be considered for permanent implant. Pain intensity, medication usage, and other multidimensional pain outcomes will be collected. The timing of these will be at baseline, end of the SCS trial and at 3-, 6-, and 12-month visits. Incidence of adverse events will be collected throughout the study duration. DISCUSSION: The results of this feasibility study will validate the efficacy and safety of DeRidder Burst-SCS stimulation in the cervical spine. The results obtained in this study will potentially be used to generate a level 1 evidence-based study with formal statistical hypotheses testing. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT03159169.

Cascade Programming for 10 kHz Spinal Cord Stimulation: A Single Center Case Series of 114 Patients With Neuropathic Back and Leg Pain.

OBJECTIVE: Ten kilohertz spinal cord stimulation (SCS) is usually initiated in a single-bipolar configuration over the radiological reference point T9/T10 intervertebral disc space for neuropathic back and leg pain. Cascade is a duty-cycled, multi-bipolar contact configuration across an entire eight-contact lead. Potential advantages by using a broader area of SCS coverage include mitigation against minor lead migration and a reduction in the need for reprogramming. We report here the results of a retrospective case series of 114 patients using Cascade. MATERIALS AND METHODS: Retrospective data were collected over two years. We selected patients with neuropathic back with or without/leg pain who had a trial of SCS. Pain assessments using Numerical Rating Scales (NRS) and Patient Global Impression of Change (PGIC) scores were collected at baseline, six months, and last follow-up beyond 12 months (mean 15.1 months). Patients were programmed with 10 kHz SCS using Cascade during the trial, which was continued unless reporting inadequate pain relief. Morbidity and deviations from Cascade programming were also obtained. RESULTS: At six months, 87 of 97 (90.6%) patients with active devices were using Cascade and 58 of 72 (81%) patients at the last follow-up >12 months. There was a significant reduction in back NRS (8.3 vs. 3.9 [p < 0.0001], N = 97) and leg pain (7.53 vs. 3.83 [p < 0.0001], N = 77) at 6 months and last follow-up >12 months back (8.3 vs. 3.95 [p < 0.0001] N = 72), leg (7.53 vs. 3.534 [p < 0.0001], N = 58). The PGIC score was 6 of 7 or all of 7 in 72% of patients (70/97) at six months and in 68% (49/72) of patients at the last follow-up beyond 12 months. CONCLUSION: Cascade is an effective programming methodology that may have benefits over a single-bipole configuration for 10 kHz SCS, particularly during a trial of stimulation. Results from this study suggest it is a durable program for patients with neuropathic back and leg pain.

Explant rates of electrical neuromodulation devices in 1177 patients in a single center over an 11-year period.

INTRODUCTION: The publication of explant rates has established risk factors and a definitive objective outcome of failure for spinal cord stimulation (SCS) treating neuropathic pain. We present a UK study analyzing explants of electrical neuromodulation devices for different conditions over 11 years in a single center specializing in neuromodulation. METHODS: A retrospective analysis was performed using a departmental database between 2008 and 2019. Explants were analyzed according to condition, mode of stimulation and other demographics using logistic regression and Kaplan-Meier graphs with log-rank (Mantel-Cox) test. RESULTS: Out of a total of 1177 patients, the explant rate was 17.8% at 5 years and 25.2% at 10 years. Loss of efficacy was the most frequent reason for explant 119/181 (65%). Multivariant regression analysis indicated patients with back pain without prior surgery had a reduced risk of explant (p=0.03). Patients with SCS systems that had 10 kHz, options of multiple waveforms, and rechargeable batteries also had a decreased risk of explant (p<0.001). None of these findings were confirmed when comparing Kaplan-Meier graphs, however. Contrary to other studies, we found gender and age were not independent variables for explant. CONCLUSION: These data contribute to a growing list of explant data in the scientific literature and give indications of what factors contribute to long-term utilization of electrical neuromodulation devices.

Comparison of Paresthesia Mapping to Anatomical Placement in Burst Spinal Cord Stimulation: Initial Trial Results of the Prospective, Multicenter, Randomized, Double-Blinded, Crossover, CRISP Study.

INTRODUCTION: In this prospective, multicenter, double-blinded, randomized, crossover study, we compared the therapeutic efficacy of burst SCS delivered using a lead implanted with the paresthesia mapping approach to a lead implanted with an anatomic placement approach. MATERIALS AND METHODS: Subjects with chronic low back pain were implanted with two leads, one using paresthesia-mapping approach (PM) and the second using anatomical placement procedure (AP). Stimulation contacts were chosen using the standard intraoperative paresthesia-testing procedure for the paresthesia-mapped lead or an activated bipole overlapping the T9-T10 junction for the anatomical lead. Amplitude for either lead was selected such that no sensory percepts were generated. Subjects were assessed at baseline and after a trial period during which they tested each lead for two weeks in random order. Eligible subjects had the option to receive permanent implants using their preferred AP or PM approach at end-of-trial. RESULTS: Of the 53 subjects who completed both trial periods, 43 (81.1%) experienced at least 50% back pain relief with at least one lead. Nearly half of these (20; 46.5%) were profound responders who experienced at least 80% back pain relief with either leads. Primary and secondary outcomes, at the end of trial, showed significant improvements for both AP and PM leads from baseline yet were not significantly different from each other. DISCUSSION: The trial results of this study suggest that similar clinical outcomes can be achieved in burst SCS when performing lead placement either using paresthesia mapping or anatomical placement with imaging references.

Sphenopalatine Ganglion Pulsed Radiofrequency for the Treatment of Refractory Chronic SUNCT and SUNA: A Prospective Case Series.

OBJECTIVES: We aimed to evaluate the safety and effectiveness of sphenopalatine ganglion pulsed radiofrequency (SPG-PRF) for the treatment of patients with refractory chronic short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and with cranial autonomic symptoms (SUNA). BACKGROUND: SPG-PRF is a minimally invasive, non-neurodestructive procedure already tested in refractory chronic cluster headache with mixed outcomes. However, no data have been produced in SUNCT/SUNA. METHODS: This was a prospective clinical audit of outcomes. Consecutive patients with chronic SUNCT/SUNA refractory to medical treatments and treated with SPG-PRF, were included in the analysis. The SPG-PRF was performed percutaneously via a lateral, infra-zygomatic approach. Responders were defined as patients with a reduction in number and/or severity of headache episodes by ≥30% for ≥3 months. Responders to the first procedure were offered to have the treatment repeated. RESULTS: Nine patients (6 female) were analyzed. After a median follow-up of 30 months (range 2-30), 7 patients were considered responders to the treatment (77.8%) for a median of 6 months (range: 4-10), 1 patient obtained 40% improvement for 2 months, and 1 patient did experience any improvement. No procedure-related immediate or delayed side effects were reported. Three patients (33.3%) experienced a worsening of the head pain for 2-4 weeks immediately after the procedure. Four responders had SPG-PRF repeated; a reproducible response was obtained in two of them. CONCLUSIONS: In our small series of patients with refractory chronic SUNCT/SUNA, SPG-PRF was a safe and effective treatment modality. The potential reproducible positive effect of subsequent treatments may prevent or delay the use of more invasive and costly interventions for at least a proportion of these patients.

Multicentre, double-blind, randomised, sham-controlled trial of 10 khz high-frequency spinal cord stimulation for chronic neuropathic low back pain (MODULATE-LBP): a trial protocol.

INTRODUCTION: Chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population. METHODS: This is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient. DISCUSSION: The outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018. DISCLAIMER: The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication. ROLES AND RESPONSIBILITIES: AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.

Effectiveness of "Transgrade" Epidural Technique for Dorsal Root Ganglion Stimulation. A Retrospective, Single-Center, Case Series for Chronic Focal Neuropathic Pain.

BACKGROUND: The recent interest in targeting the dorsal root ganglion (DRG) has led to the development of new techniques of electrode placement. In this article, we describe a new "Transgrade" approach to the DRG, accessing the contralateral interlaminar space and steering the lead out the opposite foramen. OBJECTIVES: The purpose of this study was to evaluate the Transgrade technique to the DRG in the management of focal neuropathic pain, predominately complex regional pain syndrome in terms of efficacy and safety. STUDY DESIGN: A retrospective, observational review of all patients selected for DRG stimulation using the Transgrade technique to the DRG. SETTING: Pain Management and Neuromodulation Centre, Guys and St. Thomas NHS Foundation Trust, London, United Kingdom. METHODS: Data were taken from a hospital password-protected database. All patients were contacted by telephone for Numeric Rating Scale (NRS-11) score, Patient Global Impression of Change (PGIC) score, and complications. A patient responder was defined as having a PGIC score of 6 or 7, and a 2-point reduction from baseline NRS-11. RESULTS: A total of 39 patients (46% women) with a mean age of 46 years (± 2) underwent a trial of DRG stimulation that resulted in an implantation rate of 82% (32 of 39). The responder rates, according to NRS-11 and PGIC results, were 87% (28 of 32) at 6 weeks and 66% (21 of 32) at a mean of 18 months (± 1.8) follow-up. Pocket pain was the most common complication, occurring in 7 of 32 (22%) patients, and the lead migration rate was 3 out of 57 leads placed (5.2%). A burst protocol was the favored method of stimulation in the majority of patients, 25 of 32 (78%). LIMITATIONS: Retrospective nature of design, small sample size. CONCLUSIONS: The Transgrade technique of placing DRG leads offers an alternative method that is safe and effective. New methods of stimulation to the DRG offer more choice and potentially better efficacy for patients with chronic neuropathic pain. KEY WORDS: Neuromodulation, dorsal root ganglion, neuropathic pain, complex regional pain syndrome, spinal cord stimulation, chronic pain, implantable neurostimulators, spinal nerve root stimulation.

Guideline of guidelines: bladder pain syndrome.

OBJECTIVES: Bladder pain syndrome (BPS) is a debilitating condition which can be difficult to diagnose and treat due to the lack of consensus on aetiology, definition, and management. The aim of this review is to summarise the findings from major national and international guidelines on the management of BPS, highlighting areas of disagreement and uncertainty. METHODS: We performed a Medline/PubMed search from 1st January 2000 to 31st December 2017 in order to identify relevant guidelines addressing BPS/interstitial cystitis. We also manually searched the websites of major national and international societies. The following guidelines were included in this review: European Association of Urology, American Urological Association, International Society for the Study of BPS, International Consultation on Incontinence, International Continence Society, East Asian guideline, Royal College of Obstetricians and Gynaecologists/British Society of Urogynaecology, and the Canadian Urological Association. RESULTS: There is disagreement between guidelines on the exact definition of BPS and the nomenclature to use to describe this condition. However, all agree that the diagnosis is dependent on the presence of pain, pressure, or discomfort, in addition to at least one urinary symptom, in the absence of other diseases that could cause pain. Exclusion of other pathology that could cause similar symptoms requires thorough evaluation, and is recommended in all guidelines. There is also disparity in the recommended diagnostic investigation of BPS, with hydrodistension and bladder biopsy either recommended, considered optional, or not recommended, by different guidelines. It is accepted that BPS can be diagnosed clinically, without invasive investigation, but cystoscopy and diagnostic hydrodistension aids sub-typing of patients and may help direct treatment strategies. Patients should be phenotyped in order to direct multimodal treatment (including behavioural, physical, emotional, and psychological therapy), and treatments should follow a stepwise approach starting with the most conservative. Although widely performed, hydrodistension as a therapeutic strategy has a limited evidence base and is unlikely to provide long-term resolution of symptoms CONCLUSION: There are multiple national and international guidelines for the diagnosis and management of BPS, and this review has highlighted the differences in nomenclature, definitions, and recommended diagnostic tests between guidelines. The overall evidence base for the majority of treatments for BPS/IC is of low-quality, and larger randomised trials are required to more accurately inform guideline recommendations and clinical management of this complex group of patients.

Prospective, Randomized, Sham-Control, Double Blind, Crossover Trial of Subthreshold Spinal Cord Stimulation at Various Kilohertz Frequencies in Subjects Suffering From Failed Back Surgery Syndrome (SCS Frequency Study).

INTRODUCTION: The increasing use of high frequency paresthesia-free spinal cord stimulation has been associated with improved outcomes in the therapy of neuropathic pain. What is unknown is the effect of varying frequency on pain relief and the placebo effect. MATERIALS AND METHODS: This is a prospective, randomized, sham-controlled double blind crossover study. Subjects with predominantly axial low back pain undergoing spinal cord stimulation therapy for failed back surgery syndrome were randomized to sham, 1200 Hz, 3030 Hz, and 5882 Hz with a four-phase crossover design over 12 weeks. RESULTS: Twenty-four patients were randomized in the study. The mean low back pain score at baseline was 7.75. The mean low back pain scores on a 10 cm visual analog scale during the randomized crossover phase were 4.83, 4.51, 4.57, and 3.22, for sham, 1200 Hz, 3030 Hz, and 5882 Hz, respectively, with the lowest low back pain score observed in the 5882 Hz frequency group (p = 0.002). Of note, sham stimulation resulted in a reduction of pain by -2.92 cm and was not significantly different from stimulation at 1200 Hz and 3030 Hz. CONCLUSIONS: This randomized crossover study demonstrated that 5882 Hz stimulation can produce significant pain relief for axial low back pain compared with lower frequencies and sham stimulation. Sham stimulation produced similar analgesic effects to 1200 Hz and 3030 Hz and this effect may influence future neuromodulation clinical trial designs.

Long-Term Improvements in Chronic Axial Low Back Pain Patients Without Previous Spinal Surgery: A Cohort Analysis of 10-kHz High-Frequency Spinal Cord Stimulation over 36 Months.

Objective: This prospective, open-label study was designed to evaluate the long-term effectiveness of 10-kHz high-frequency spinal cord stimulation (SCS) in the treatment of chronic axial low back pain with no history of spinal surgery. Methods: Patients with chronic low back pain without previous spinal surgery underwent assessment by a multidisciplinary pain and surgical team to confirm eligibility. After a successful temporary trial of 10-kHz HF-SCS therapy, defined by ≥50% back pain reduction, enrolled subjects underwent permanent system implantation and were followed up for 36 months. Outcome measures consisted of a 100-mm visual analog scale (VAS) for pain intensity, the Oswestry Disability Index (ODI), and a standard measure of health-related quality of life. Results: Twenty-one patients satisfied the inclusion/exclusion criteria. Following a temporary trial, 20 of 21 (95%) subjects were implanted with a pulse generator, and 17 of 20 reached the 36-month time point. From baseline to 36 months, the average VAS pain intensity decreased from 79 ± 12 mm to 10 ± 12 mm, the average ODI score decreased from 53 ± 13 to 19.8 ± 13, and use of opioids decreased from 18 subjects to two subjects. One subject was deceased, unrelated to the study, one subject was explanted due to loss of effectiveness, and one subject was lost to follow-up. Conclusions: These results suggest that 10-kHz high-frequency SCS may provide significant, long-term back pain relief, improvement in disability and quality of life, and reduction in opioids for nonsurgical refractory back pain.

Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial.

BACKGROUND: Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent µ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia. METHODS: Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 µg h-1 for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively. RESULTS: A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min (P=0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine (P=0.009). At three months, no differences between groups were noted. CONCLUSIONS: Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-Concept Study.

OBJECTIVE: To explore the effectiveness of 10 kHz high frequency spinal cord stimulation (HF10 therapy) treatment of chronic low back pain in patients who have not had spinal surgery. METHODS: Patients with chronic low back pain without prior spinal surgery were evaluated by a team of spine surgeons to rule out any spinal pathology amenable to surgical interventions and by a multidisciplinary pain team to confirm eligibility for the study. After a successful (>50% back pain reduction) trial of HF10 therapy, enrolled subjects underwent permanent system implantation and were followed-up one year post-implant. RESULTS: About 95% of the enrolled subjects (20/21) received the permanent system. At 12 months post-implant, both back pain VAS score and ODI were significantly reduced compared with baseline values (by 73% and 48%, respectively); an estimated quality-adjusted life year gain of 0.47 and a reduction in opioid use by 64% was observed. Four more patients among those unable to work at baseline due to back pain were employed at 12 months post-implant. There were no serious adverse events. CONCLUSION: HF10 therapy may provide significant back pain relief, reduction in disability, improvement quality of life, and reduction in opioid use in chronic low back pain not resulting from spinal surgery.

Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: a retrospective case series.

BACKGROUND: Paresthesia-free cervical 10 kHz spinal cord stimulation (HF10 SCS) may constitute a novel treatment modality for headache disorders, when pharmacological approaches fail. We report the results of a retrospective analysis assessing the long-term safety, tolerability and efficacy of HF10 SCS in a group of patients with chronic refractory primary headache disorders. FINDINGS: Four patients with chronic migraine (CM), two with chronic SUNA (Short-lasting Unilateral Neuralgiform headache attacks with Autonomic symptoms) and one with chronic cluster headache (CCH) refractory to medical treatments, were implanted with cervical HF10 SCS. Pre- and post-implantation data were collected from the medical notes and from headache charts. At an average follow-up of 28 months (range: 12-42 months) we observed an improvement of at least 50 % in headache frequency and/or intensity in all CM patients. One SUNA patient became pain free and the other reported at least 50 % improvement in attacks frequency an duration. The CCH patient reported a significant reduction in CH attacks duration. Two patients underwent a surgical revision due to lead migration. CONCLUSIONS: Paresthesia-free high cervical HF10 SCS appears to be a long-term safe and likely effective therapeutic approach for patients with chronic refractory primary headache disorders. These results warrant further prospective studies in larger series of patients.

The use of 10-kilohertz spinal cord stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management.

OBJECTIVE: It is the purpose of this study to document our experience with the use of a 10-kHz high-frequency spinal cord stimulation (SCS) device for the relief of neuropathic pain of the upper and lower limbs. MATERIALS AND METHODS: A retrospective chart review was performed of all patients treated with the 10-kHz high-frequency SCS system for neuropathic pain (upper or lower limb) refractory to conventional treatment. All patients underwent a trial with one or two eight-contact percutaneous leads using 50-Hz traditional stimulation. If ≥ 80% paresthesia coverage of the painful area with traditional SCS was obtained, high-frequency 10-kHz SCS was used. Patients who had a significant reduction in pain score (≥ 50%) at the end of the trial received a permanent implant and were then followed for up to six months. Outcome measures included a numeric rating scale for pain, the Brief Pain Inventory, health-related quality of life (EQ-5D), the Pain Catastrophizing Scale, and patient satisfaction. RESULTS: Fifteen patients completed a trial of high-frequency 10-kHz SCS. Eleven patients proceeded to permanent implantation. Ten of the 11 patients who proceeded to full implantation had significant reductions in all of the collected outcome variables at one, three, and six months. CONCLUSIONS: In this small cohort of patients, high-frequency 10-kHz SCS reduced pain and improved quality of life. However, before we can conclude that high-frequency 10-kHz SCS for neuropathic pain of the upper and lower extremities is efficacious, a large-scale multicenter observational study should be performed to corroborate our small retrospective study.