Objective
The objective of this prospective, open‐label, multicenter European clinical trial was to quantify the efficacy and safety of a spinal cord stimulation (SCS) system that utilizes ...high‐frequency (up to 10 kHz) waveforms, which do not produce paresthesia, for the treatment of chronic, intractable pain of the back and/or limbs.
Material and Methods
Eighty‐three patients, with significant back pain, were recruited for a trial of high‐frequency stimulation through two percutaneous eight‐contact epidural leads. Patients' pain ratings, disability, sleep disturbances, and satisfaction, as well as complication rates, were assessed for up to six months.
Results
After a trial period, 88% (72 out of 82) of patients reported a significant improvement in visual analog scale (VAS) scores and underwent permanent implantation of the high‐frequency SCS system. Mean back pain VAS of 8.4 was reduced to 2.7 at six months (p< 0.001). Mean leg pain VAS of 5.4 was reduced to 1.4 at six months (p< 0.001). Seventy‐four percent of patients had greater than 50% back pain relief at six months. There were significant improvements in Oswestry disability score and sleep, and reductions in pain medication use. Adverse events observed were those seen with conventional SCS therapy—lead migration, wound infection, and pain around implant site.
Conclusions
In a cohort of patients with difficult‐to‐treat chronic back pain, high‐frequency SCS provided significant and sustained low back pain and leg pain relief to more than 70% of treated subjects. Notably, this was achieved without paresthesia. Patients also experienced significant improvement in disability and sleep. Overall, the results confirm a favorable safety and efficacy profile of the high‐frequency SCS system.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018.
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.
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.
Introduction:
Chronic migraine (CM), the suffering of 15 or more headache days with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global population. CM is the most common disorder ...faced by experts in tertiary headache centers. When resistant to conventional medical treatment and prophylactic medication this condition is known as refractory chronic migraine (RCM). RCM is one of the greatest challenges in headache medicine.
Areas covered:
State-of-the-art and future medical treatments of chronic migraine include: OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery systems of Sumatriptan, a well-established drug treatment for acute migraine), CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and BOL-148. The role for neuromodulation, the application of targeted electrical stimulation, will be examined.
Expert opinion:
Medication overuse headache (MOH) is now recognized to be a major factor in many cases of both chronic and refractory chronic migraine. MOH must be addressed prior to evaluating the effectiveness of new preventative and prophylactic treatment approaches. Innovative new drugs and electrical neuromodulation are promising CM treatments. Future studies must carefully screen patients and acquire data that can lead to personalized, tailored treatment strategies.
Among all the causes of chronic low back pain, myofascial pain syndrome of the spinal stabilizer muscles is one of the most frequent, yet underconsidered sources of pain. The purpose of this ...prospective, randomized, double-blind, controlled trial was to evaluate the efficacy of type-A botulinum toxin (BTX-A) in relieving myofascial pain in patients experiencing mechanical low back pain due to bilateral myofascial pain syndrome involving the iliopsoas and/or the quadratus lumborum muscles.
Each of the 27 enrolled patients received a bilateral, fluoroscopically guided injection in the affected muscle(s) to randomly deliver BTX-A in one side of the low back and a control drug (randomly constituted by NaCl 0.9% or bupivacaine 0.25%) in the opposite side. To evaluate the effects of treatment on daily life activities and psychologic status, 5 different questionnaires were administered (Hospital Anxiety and Depression scale HAD-A and HAD-D, Lattinen, Oswestry, and Spielberger State-Trait Anxiety Index).
BTX-A injection did not significantly reduce visual analog scale scores more than treatment with NaCl or bupivacaine in the contralateral side; furthermore, the treatments administered did not result in a significant improvement of patients' daily life activities or psychologic status. Although a trend toward a decrease in postintervention visual analog scale scores could be recognized in all low back sides, this trend was significant only in the sides treated with BTX-A.
BTX-A seems to provide significant postintervention pain relief. However, considering its high cost and the small differences compared with control treatments, its use should be reserved only for patients with pain refractory to other invasive treatments.
Objective: Botulinum toxin is a neurotoxin that has been widely used in chronic pain for the treatment of multiple conditions with a component of localized muscle spasm. Recent studies suggest that ...botulinum toxin is effective in the treatment of neuropathic pain syndromes such as post‐herpetic neuralgia.
Case Report: We report the case of a 67‐year‐old man who underwent atypical segmentectomy of a right lower lobe lung nodule. The patient was referred to our pain management department with a of 2‐year history persistent pain along the thoracotomy scar having a predominantly neuropathic component, refractory to standard treatments. He was successfully treated with subcutaneous botulinum toxin type A.
Discussion: On the basics of our own experience and on the analysis of the reports published in the literature, fractioned subcutaneous injections of botulinum toxin may be useful for the treatment of various chronic localized pain conditions including chronic post‐thoracotomy pain.
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.
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