Neuropathic Leg Pain Research Articles

Pulse Intensity Effects of Burst and Tonic Spinal Cord Stimulation on Neural Responses to Brushing in Patients With Neuropathic Pain

ObjectivesTonic spinal cord stimulation (SCS) is accompanied by paresthesia in affected body regions. Comparatively, the absence of paresthesia with burst SCS suggests different involvement of the dorsal column system conveying afferent impulses from low-threshold mechanoreceptors. This study evaluated cortical activation changes during gentle brushing of a pain-free leg during four SCS pulse intensities to assess the effect of intensity on recruitment of dorsal column system fibers during burst and tonic SCS. Materials and MethodsTwenty patients using SCS (11 burst, nine tonic) for neuropathic leg pain participated. Brushing was administered to a pain-free area of the leg during four SCS intensities: therapeutic (100%), medium (66%), low (33%), and no stimulation. Whole-brain electroencephalography was continuously recorded. Changes in spectral power during brushing were evaluated using the event-related desynchronization (ERD) method in theta (4–7 Hz), alpha (8–13 Hz), and beta (16–24 Hz) frequency bands. ResultsBrushing was accompanied by a suppression of cortical oscillations in the range 4–24 Hz. Stronger intensities of burst and tonic SCS led to less suppression of 4–7 Hz and 8–13 Hz bands in parietal electrodes, and in central electrodes in the 16–24 Hz band, with the strongest, statistically significant suppression at medium intensity. Tonic SCS showed a stronger reduction in 4–7 Hz oscillations over right sensorimotor electrodes, and over right frontal and left sensorimotor electrodes in the 8–13 Hz band, compared to burst SCS. ConclusionsResults suggest that burst and tonic SCS are mediated by both different and shared mechanisms. Attenuated brushing-related ERD with tonic SCS suggests a gating of cortical activation by afferent impulses in the dorsal column, whereas burst may engage different pathways. Diminished brushing-related ERD at medium and therapeutic intensities of burst and tonic SCS points towards a nonlinear effect of SCS on somatosensory processing.

Somnolence and Dizziness During Mirogabalin Treatment in Patients With Neuropathic Pain Related to Lumbar Disease Who Switched From Pregabalin: A Retrospective Study.

Multicenter retrospective study. To investigate adverse events (AEs) in patients with neuropathic pain related to lumbar disease who switched to mirogabalin from pregabalin. This study surveyed the records of 82 patients with peripheral neuropathic leg pain related to lumbar disease who switched to mirogabalin from pregabalin. We evaluated AEs associated with pregabalin and mirogabalin, the continuation rate of mirogabalin, and the pain-relieving effect at 4 weeks after switching from pregabalin to mirogabalin. We compared patients who switched due to lack of efficacy (LoE group) and patients who switched due to AEs (AE group). The incidence rates of somnolence and dizziness with pregabalin were 12.2% and 14.6%, respectively, while the incidence rates with mirogabalin were reduced to 7.3% for somnolence and 4.9% for dizziness. The incidence of AEs with pregabalin was significantly higher in the AE group (LoE group: 11.1%, AE group 100%), especially for somnolence (LoE group: 3.2%, AE group: 47.1%) and dizziness (LoE group: 4.8%, AE: 52.9%). After switching, the incidences of AEs with mirogabalin were not significantly different between the 2 groups (LoE group: 15.9%, AE group: 23.5%), including for somnolence (LoE group: 7.9%, AE group: 5.9%) and dizziness (LoE group: 4.8%, AE group: 5.9%). There were no significant differences in continuation rate of mirogabalin or the pain-relieving effect between groups. The patients who experience somnolence and dizziness with pregabalin might be able to continue safely receiving treatment for their pain by switching to mirogabalin.

A Comparison of 1000Hz to 30Hz Spinal Cord Stimulation Strategies in Patients with Unilateral Neuropathic Leg Pain Due to Failed Back Surgery Syndrome: A Multicenter, Randomized, Double-Blinded, Crossover Clinical Study (HALO).

IntroductionMulticenter, randomized, double-blinded crossover study. The Netherlands (ClinicalTrials.gov NCT02112474). We hypothesized that the pain suppressive effects of 1000 Hz and 30 Hz spinal cord stimulation (SCS) strategies are equally effective in patients with chronic, neuropathic, unilateral leg pain after back surgery.MethodsThirty-two patients (18–70 years, minimum leg pain 50 mm on 100 mm visual analog scale (VAS), minimal back pain) were randomized (1:1) to start 1000 Hz or 30 Hz neurostimulation for 9 days. After a 5-day washout, they crossed over, for another 9 days. Primary outcome was pain suppression (mean of VAS scores 4×/day) during the crossover period. The main investigators were blinded to strategy allocation, patients were blinded to the outcome, a blinded assessor analyzed the primary outcome.ResultsThe primary outcome was analyzed in 26 patients. There was no period effect (delta 4 mm, p = 0.42, 95% CI [− 5, 13]), allowing direct intrapatient comparison of the treatment effect (delta 1 mm, p = 0.92, 95% CI [− 13, 14]). Ninety-two percent of patients in both periods experienced greater than 34% pain suppression (minimal clinically important difference, MCID). Secondary outcomes (22 patients): pain suppression and improved quality of life were sustained at 12 months; both were statistically significant and clinically relevant. Fifty percent of patients had greater than 80% pain suppression (p < 0.001).At study termination, all events were resolved; no unanticipated events were reported. Medtronic provided a grant for additional study costs.ConclusionWe conclude that our hypothesis regarding the effect of 1000 Hz and 30 Hz stimulation strategies on pain suppression was confirmed. Both stimulation strategies led to a large, sustainable, clinically relevant pain suppression and improvement in quality of life.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00268-7.

P.137 A case of leprosy in the UK

Introduction: Leprosy is a multi-system disease caused by Mycobacterium leprae. Whilst uncommon in the developed world, cases continue to rise in developing nations with up to 200,000 new cases reported annually. 1We report a case of lepromatous leprosy in a parturient residing in Scotland. Case Report: A 26-year-old primigravida presented in early pregnancy following a history of nosebleeds and widespread rash. The patient was a sickle-cell carrier but was otherwise well with no allergies. A diagnosis of lepromatous leprosy with erythema nodosum reaction was made and treatment commenced with prednisolone and combination therapy with rifampicin, clofazimine and dapsone. The pregnancy was complicated by anaemia and thrombocytopaenia with mild splenomegaly. Anaemia was thought to be secondary to Dapsone-related haemolysis, and thrombocytopaenia was thought most likely to be gestational. She developed neuropathic leg pain and hypoaesthesia but this resolved during the pregnancy. Renal and liver function remained normal and there were no symptoms or signs of autonomic dysfunction with normal postural blood pressure readings and normal ECG. After multi-disciplinary discussion, induction of labour was planned due to concerns over fetal growth. The patient was screened for SARS-CoV-2 and this was positive, though the patient remained asymptomatic. The patient was not considered to be infectious and standard infection control procedures were observed. Anaesthetic options for analgesia in labour and anaesthesia for potential operative delivery were discussed at several occasions during pregnancy and ”OAA Labour Pains” translated information sheets were given to the patient. Following induction of labour, the patient had a spontaneous vaginal delivery with no anaesthetic intervention required. Discussion: Leprosy is uncommon in developed nations but may occur in the UK as the population becomes more diverse. Leprosy raises many potential challenges for the anaesthetist including;cutaneous changes (which may be of particular significance if occurring over sites of intravenous access or lower lumbar region), neuropathies, myopathies, autonomic dysfunction, haematological derangements (including anaemia, thrombocytopaenia and agranulocytosis) and liver and renal impairment. Drug therapies for leprosy may in themselves be associated with blood dyscrasias, hepatitis, psychosis, and peripheral neuropathies. Anaesthetic management should be informed by the presence of any complications, most notable thrombocytopaenia or peripheral neuropathies. The possibility of autonomic dysfunction should be considered regardless of which anaesthetic modality is chosen and care taken to actively manage hypotension. The patient’s SARS-CoV-2 status was a further factor influencing the risk-benefit assessment of anaesthetic options in this case.

Is chronic low back pain and radicular neuropathic pain associated with smoking and a higher nicotine dependence? A cross-sectional study using the DN4 and the Fagerström Test for Nicotine Dependence.

Objective - To evaluate if a current smoking status and a higher nicotine dependence were associated with chronic low back pain and/or radicular neuropathic pain. Materials and methods- A cross-sectional study was conducted on the first eligible consecutive 120 patients. Demographic data, pain intensity, worst pain location, most distal pain radiation, the DN4 questionnaire, STarT back tool, and the Fagerström Test were collected during the initial examination. An age- and gender-matched control group (n=50), free from chronic low back pain was recruited. Results- In the chronic pain group, there was a significant difference between smokers and lifetime non-smokers in the average pain intensity (p=0.037), total DN4 score (p=0.002), STarT Back tool (p=0.006), worst pain location (p=0.023) and the most distal pain radiation (p=0.049). The mean total DN4 score increased with a corresponding increase in the number of cigarettes smoked daily (p=0.002). Current smokers had an OR of 3.071 (p=0.013) (95% CI 1.268-7.438) for developing chronic low back pain and lumbar related leg pain and an OR of 6.484 (p<0.001) (95% CI 2.323-18.099) for developing chronic radicular neuropathic leg pain. For every one-unit increase in the Fagerström test score, the likelihood for chronic low back pain and lumbar related leg pain increased by 40.71% (p=0.008) (95% CI 1.095-1.809) and for chronic radicular neuropathic leg pain increased by 71.3% (p<0.001) (95% CI 1.292-2.272). Conclusion- A current smoking status and a higher nicotine dependence were both independently associated with an increased risk for chronic low back pain and/or chronic radicular neuropathic pain.

Multicolumn spinal cord stimulation for predominant back pain in failed back surgery syndrome patients: a multicenter randomized controlled trial.

Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP. This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) at 28 sites in Europe and the Americas. If trial stimulation was successful, a multicolumn SCS system was implanted. Outcomes were assessed at baseline (before randomization) and at 1, 3, 6, and 12 months after randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability, and health-related quality of life (HRQoL). The results are posted at ClinicalTrials.gov under registration number NCT01697358. In the intent-to-treat analysis, there were more responders in the SCS group than in the OMM group (13.6%, 15/110 vs 4.6%, 5/108, difference 9% with 95% confidence interval 0.6%-17.5%, P = 0.036) at 6 months. The SCS group improved in all secondary outcomes compared with the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related adverse events through 6 months, with 11.8% (12/102) requiring surgical reintervention. Adding multicolumn SCS to OMM improved pain relief, HRQoL, and function in a traditionally difficult-to-treat population of failed back surgery syndrome patients with predominant LBP. Improvements were sustained at 12 and 24 months.

The appropriate management of persisting pain after spine surgery: a European panel study with recommendations based on the RAND/UCLA method

PurposeManagement of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.MethodsUsing the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).ResultsAppropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.ConclusionsUsing the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Spinal manipulative therapy reduces peripheral neuropathic pain in the rat.

Spinal manipulative therapy, including low-velocity variable-amplitude spinal manipulation (LVVA-SM), relieves chronic low back pain, especially in patients with neuropathic radiating leg pain following peripheral nervous system insult. Understanding the underlying analgesic mechanisms requires animal models. The aim of the current study was to develop an animal model for the analgesic actions of LVVA-SM in the setting of peripheral neuropathic pain. Adult male Sprague-Dawley rat sciatic nerve tibial and common peroneal branches were transected, sparing the sural branch (spared nerve injury, SNI). After 15-18 days, rats were assigned randomly to one of three groups (n=9 each group): LVVA-SM at 0.15-or 0.16-Hz or Control. LVVA-SM (20° flexion at the L5 vertebra with an innovative motorized treatment table) was administered in anesthetized rats for 10 min. Control rats were administered anesthesia and positioned on the treatment table. After 10, 25, and 40 min, the plantar skin of the hindpaw ipsilateral to SNI was tested for mechanical sensitivity (paw withdrawal threshold to a logarithmic series of Semmes-Weinstein monofilaments) and cold sensitivity (duration of paw lifting, shaking, and/or licking to topical acetone application). SNI produced behavioral signs of mechanical and cold allodynia. LVVA-SM reduced mechanical, but not cold, hypersensitivity compared with Control (0.15-Hz: P=0.04 at 10 min; 0.16-Hz: P<0.001 at 10 min, P=0.04 at 25 min). The analgesic effect of LVVA-SM in chronic low back pain patients with neuropathic leg pain can be reverse-translated to a rat model Video abstract: http://links.lww.com/WNR/A453.

Effect of duloxetine on neuropathic pain in patients intolerant to continuous administration of pregabalin.

Purpose: We examined duloxetine's effectiveness in the treatment of neuropathic pain in patients who were intolerant to continuous pregabalin administration. Materials and Methods: The present study is a retrospective study of patients diagnosed with neuropathic pain with neuropathic leg pain as the chief complaint. We analyzed 20 cases in which pregabalin was changed to duloxetine because of adverse effects (16 cases) or treatment failure (4 cases). The incidence of adverse events after duloxetine administration was used as the primary endpoint, with the secondary endpoint being the leg pain level based on a numerical rating scale (NRS). Results: The incidence of adverse events after starting duloxetine was 40%. Average leg pain scores measured on the NRS were 8.4±1.4, 6.4±1.4, and 4.1±2.0 at the time of the patients' first visit, pregabalin discontinuation, and after switching to duloxetine, respectively. A significant difference in NRS scores was found between the first visit and pregabalin discontinuation and also between pregabalin discontinuation and after the switch to duloxetine (p<0.05), indicating that pain decreases over time. Furthermore, NRS scores significantly declined between the patients' first visit and after the switch to duloxetine (p<0.05). The improvement in NRS score was 20±12.8% after pregabalin administration and 23±12.0% after duloxetine administration compared with baseline scores (no significant difference between pregabalin and duloxetine; p>0.05). Conclusion: When patients with neuropathic pain are unable to tolerate pregabalin because of adverse effects, changing the medication to duloxetine may be an option.

Efficacy of Duloxetine in Chronic Low Back Pain with a Neuropathic Component: A Randomized, Double-blind, Placebo-controlled Crossover Trial.

Among patients with chronic low back pain (CLBP), approximately 37% show signs of a neuropathic pain component (radicular pain). Treatment of this condition remains challenging. Therefore, the current study aimed to investigate the efficacy of duloxetine in the treatment of CLBP patients with neuropathic leg pain. The study was conducted as a prospective, randomized, placebo-controlled, double-blind crossover trial. CLBP with a visual analog scale (VAS) score greater than 5 and a neuropathic component that was assessed clinically and by the painDETECT questionnaire (score > 12) were required for inclusion. Patients were randomly assigned to either duloxetine or placebo for 4 weeks followed by a 2-week washout period before they crossed over to the alternate phase that lasted another 4 weeks. Duloxetine was titrated up to 120 mg/day. The primary outcome parameter was mean VAS score during the last week of treatment in each phase (VAS(week4)). Of 41 patients, 21 patients completed both treatment phases. In the intention-to-treat analysis (n = 25), VAS(week4) was significantly lower in the duloxetine phase compared with placebo (4.1 ± 2.9 vs. 6.0 ± 2.7; P = 0.001), corresponding to an average pain reduction of 32%. The painDETECT score at the end of each treatment phase was significantly lower in the duloxetine phase compared with placebo (17.7 ± 5.7 vs. 21.3 ± 3.6 points; P = 0.0023). Adverse events were distributed equally between the duloxetine (65%) and placebo phases (62%) (P = 0.5). In this crossover study, duloxetine proved to be superior to placebo for the treatment of CLBP with a neuropathic leg pain.

Pregabalin for Refractory Radicular Leg Pain due to Lumbar Spinal Stenosis: A Preliminary Prospective Study.

We investigated the efficacy of pregabalin (PGB) for neuropathic leg pain in lumbar spinal stenosis (LSS) patients with disturbed activities of daily living (ADL)/quality of life (QOL) in a prospective observational study. Subjects were a total of 104 LSS patients with neuropathic pain (NeP) in leg and neurological intermittent claudication (IMC) refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) for at least a month. NeP was identified using screening tool, Pain DETECT questionnaire. Visual analog scale (VAS) scores and responses to the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were assessed before and 6 weeks after PGB treatment initiation. Changes in IMC distance and adverse events were also recorded. PGB significantly improved their VAS scores for pain and sleep quality (P < 0.001). With respect to JOABPEQ, significant improvements were observed with regard to the following dimensions: pain-related disorders (P < 0.01), lumbar spine dysfunction (P = 0.031), gait disturbance (P = 0.028), and psychological disorders (P = 0.014). The IMC distance showed an improvement tendency after PGB treatment, albeit with no significance (P = 0.063). Minor adverse events such as dizziness were observed. PGB can be effective for neuropathic leg pain refractory to NSAIDs in LSS patients, resulting in not only pain control but also improving lower back pain-related ADL/QOL scores.

Straight leg raise treatment for individuals with spinally referred leg pain: effects on sciatic nerve excursion

Background: Individuals with spinally referred leg pain may have 3 different causes of their pain: somatic referral, radicular pain and radiculopathy. Straight leg raise (SLR) treatment has been advocated for the assessment and treatment of neuropathic leg pain, but little is known about the changes to the biomechanical properties of the nervous tissue after treatment.

Physiotherapist prescribing in lower back pain: A case study

Changes to legislation have allowed physiotherapists to train as independent prescribers, and the first cohorts qualified in early 2014. Some will be upgrading their supplementary prescribing qualifications, while others will be training for the first time in prescribing. This article discusses the role of the extended scope physiotherapist as an independent prescriber in a specialist musculoskeletal setting. The case study outlines the assessment and treatment of a patient with lower back pain and neuropathic leg pain, and details the prescribing issues involved in the overall management.

Cauda Equina Syndrome Associated with Dural Ectasia in Chronic Anlylosing Spondylitis

Cauda equina syndrome (CES) associated with dural ectasia is a rare neurologic complication in patients with longstanding ankylosing spondylitis (AS). We report a 68-year-old male with a 30-year history of AS who presented a typical symptom and signs of progressive CES, urinary incontinence and neuropathic pain of the lumbosacral radiculopathy. Computed tomography (CT) and magnetic resonance imaging (MRI) findings showed the unique appearances of dural ectasia, multiple dural diverticula, erosion of posterior element of the lumbar spine, tethering of the conus medullaris and adhesion of the lumbosacral nerve roots to the posterior aspect of the dural ectasia. Considering the progressive worsening of the clinical signs, detethering of the conus medullaris through resection of the filum terminale was performed through a limited laminectomy. However, the urinary incontinence did not improve and there was a partial relief of the neuropathic leg pain only. The possible pathogenetic mechanism of CES-AS and the dural ectasia in this patient with longstanding AS are discussed with a literature review.

Bilateral neuropathic leg pain a manifestation of a rare disorder: Cowden syndrome - a case report

Bilateral neuropathic leg pain a manifestation of a rare disorder: Cowden syndrome - a case report

Multi-target neurostimulation for adequate long-term relief of neuropathic and nociceptive chronic pain components

Successful treatment of chronic pain for patients with failed back surgery syndrome can be extremely complicated. These patients require careful and individualized clinical assessment, as they often present with mixed pain syndromes that involve both neuropathic and nociceptive components. The distinct types of pain involved in such cases may require combined treatments from individual interventions that are analgesically independent and specific for each type of pain involved. Neuromodulation by electric stimulation at appropriately chosen targets and combinations may be an important option to consider for such patients. We present a case of combined debilitating axial nociceptive spinal pain and bilateral neuropathic leg pain in a patient after 14 failed back operations. A combination of spinal cord stimulation (SCS) and deep brain stimulation in the periventricular gray (PVG) have successfully provided the patient with complete relief of both components of his chronic pain condition, after all other pain management options had been exhausted. By alternating activation of each implanted stimulator separately and in conjunction, we were able to demonstrate a clinically independent analgesic character for each stimulation system, each specific to a particular type of pain. The SCS provided complete relief of the neuropathic pain component, without affecting the nociceptive component at all. The PVG stimulation provided complete relief of the nociceptive component, without affecting the neuropathic component at all. In combination, there was complete relief of the total chronic pain condition. There appeared to be no overlapping or synergistic effect between the two neuromodulation systems in the patient. The patient has had prolonged complete relief from his chronic pain condition with the combined neuromodulation intervention over 22 years of follow-up.

Arachnoid ossificans of thoracolumbosacral spine in the advanced ankylosing spondylitis: a case report

Arachnoid ossificans is a rare type of chronic arachnoiditis characterised by the presence of calcification or ossification of the dura and arachnoid. There are a few reports of these findings in relation to various disease entities, but only one case has been reported in relation to ankylosing spondylitis. We describe a 76-year-old man of ankylosing spondylitis with arachnoiditis ossificans, who has suffered from low back pain and neuropathic leg pain.

Spinal Cord Stimulation vs. Conventional Medical Management: A Prospective, Randomized, Controlled, Multicenter Study of Patients with Failed Back Surgery Syndrome (PROCESS Study)

Introduction. Since its first application in 1967, numerous case series indicate that spinal cord stimulation (SCS) is an effective treatment for the management of failed back surgery syndrome (FBSS). However, only one randomized controlled trial has demonstrated that SCS provides more effective pain relief than re-operation and conventional medical management. The PROCESS randomized, controlled, multicenter trial aims to assess the clinical effectiveness and cost-effectiveness of SCS when added to conventional medical management compared to conventional medical management alone in patients with FBSS. Methods/Design. A total of 100 FBSS patients with predominantly neuropathic leg pain will be recruited from 12 centers and randomized to receive either conventional medical management alone or in combination with SCS for a period of 24months. Patients will be evaluated at 1, 3, 6, 9, 12, 18, and 24months. At the 6-month visit, patients will be classified as successful (≥ 50% pain relief in the legs) or unsuccessful (<50% pain relief in the legs). If the results of the randomized treatment are unsuccessful, patients can cross over to the alternative treatment arm. Discussion. This paper highlights the rationale, design, methods, and challenges of an ongoing prospective, randomized, controlled, multicenter clinical trial that has been undertaken to obtain conclusive evidence of the clinical efficacy and cost-effectiveness of an SCS system in patients with FBSS.