Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: A review

Context

Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain.

Objective

To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy.

Methods

A MEDLINE search was performed using following terms: “Spinal cord injury”, “Neuropathic pain”, “Brain stimulation”, “Deep brain stimulation” (DBS), “Motor cortex stimulation” (MCS), “Transcranial magnetic stimulation” (TMS), “Transcranial direct current stimulation” (tDCS), “Cranial electrotherapy stimulation” (CES).

Results

Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation – tDCS – applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI.

Conclusion

A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.     

Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): A sham-controlled crossover study

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP.Design: A double-blind, randomized, crossover and sham-controlled study.Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan.Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15.Interventions: tsDCS (anodal or sham, 2.0 mA, 20’, five days) delivered over the thoracic spinal cord (T10-T12).Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T₀), at the end of the stimulation (T₁), after one week (T₂), one month (T₃) and two months (T₄).Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T₁, P = .0137; T₄, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time.Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.     

Transcranial direct current stimulation (tDCS) paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: A pilot study

Objective: Our goal was to determine if pairing transcranial direct current stimulation (tDCS) with rehabilitation for two weeks could augment adaptive plasticity offered by these residual pathways to elicit longer-lasting improvements in motor function in incomplete spinal cord injury (iSCI).

Design: Longitudinal, randomized, controlled, double-blinded cohort study.

Setting: Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Participants: Eight male subjects with chronic incomplete motor tetraplegia.

Interventions: Massed practice (MP) training with or without tDCS for 2 hrs, 5 times a week.

Outcome Measures: We assessed neurophysiologic and functional outcomes before, after and three months following intervention. Neurophysiologic measures were collected with transcranial magnetic stimulation (TMS). TMS measures included excitability, representational volume, area and distribution of a weaker and stronger muscle motor map. Functional assessments included a manual muscle test (MMT), upper extremity motor score (UEMS), action research arm test (ARAT) and nine hole peg test (NHPT).

Results: We observed that subjects receiving training paired with tDCS had more increased strength of weak proximal (15% vs 10%), wrist (22% vs 10%) and hand (39% vs. 16%) muscles immediately and three months after intervention compared to the sham group. Our observed changes in muscle strength were related to decreases in strong muscle map volume (r=0.851), reduced weak muscle excitability (r=0.808), a more focused weak muscle motor map (r=0.675) and movement of weak muscle motor map (r=0.935).

Conclusion: Overall, our results encourage the establishment of larger clinical trials to confirm the potential benefit of pairing tDCS with training to improve the effectiveness of rehabilitation interventions for individuals with SCI.

Trial Registration: NCT01539109     

Analgesic efficacy of cerebral and peripheral electrical stimulation in chronic nonspecific low back pain: a randomized,double-blind,factorial clinical trial

Background

Chronic non-specific low back pain is a major socioeconomic public health issue worldwide and, despite the volume of research in the area, it is still a difficult-to-treat condition. The conservative analgesic therapy usually comprises a variety of pharmacological and non-pharmacological strategies, such as transcutaneous electrical nerve stimulation. The neuromatrix pain model and the new findings on the process of chronicity of pain point to a higher effectiveness of treatments that address central rather than peripheral structures. The transcranial direct current stimulation is a noninvasive technique of neuromodulation that has made recent advances in the treatment of chronic pain. The simultaneous combination of these two electrostimulation techniques (cerebral and peripheral) can provide an analgesic effect superior to isolated interventions. However, all the evidence on the analgesic efficacy of these techniques, alone or combined, is still fragmented. This is a protocol for a randomized clinical trial to investigate whether cerebral electrical stimulation combined with peripheral electrical stimulation is more effective in relieving pain than the isolated application of electrical stimulations in patients with chronic nonspecific low back pain.

Methods/Design

Ninety-two patients will be randomized into four groups to receive transcranial direct current stimulation (real/sham) + transcutaneous electrical nerve stimulation (real/sham) for 12 sessions over a period of four weeks. The primary clinical outcome (pain intensity) and the secondary ones (sensory and affective aspects of pain, physical functioning and global perceived effect) will be recorded before treatment, after four weeks, in Month 3 and in Month 6 after randomization. Confounding factors such as anxiety and depression, the patient’s satisfaction with treatment and adverse effects will also be listed. Data will be collected by an examiner unaware of (blind to) the treatment allocation.

Discussion

The results of this study may assist in clinical decision-making about the combined use of cerebral and peripheral electrical stimulation for pain relief in patients with chronic low back pain.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT01896453","term_id":"NCT01896453"}}NCT01896453     

A review of sacral nerve stimulation for the treatment of faecal incontinence

Sacral nerve stimulation is an emerging surgical technique that uses chronic low-level electrical stimulation, applied to the nerves of the sacral plexus, to produce a clinically beneficial physiological effect on the lower bowel, pelvic floor and anal canal. Faecal incontinence is common, maximal conservative therapy may improve some patients but many require surgery. Results are variable and often unsatisfactory and further options are limited, the traditional end-point being the formation of a colostomy. Sacral nerve stimulation appears to be an alternative treatment that is successful, has low morbidity, is maintained in the medium term and associated with an improved quality of life. The technique has the advantage of a minimally invasive test procedure with high predictive value and the surgery is minor. The underlying mechanism of action although predominately neurological in nature remains to be determined. Precise patient selection is currently unclear however, results are superior to other techniques.     

A simple and cost-effective method of fixation of deep brain stimulation (DBS) electrode

Summary Unplanned migration of a deep brain stimulation (DBS) electrode after accurate placement at the intended target can result in a poor surgical outcome and added cost to the procedure. There are various fixation methods described in the literature. The authors describe the use of a modified burr-hole cover which serves as a simple and cost-effective method of fixation of the DBS lead with excellent results. Correspondence: Dr Wai Hoe Ng, Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.     

Use of gabapentin and pregabalin for pruritus and neuropathic pain associated with major burn injury: A retrospective chart review

Introduction

Pruritis after burn is one of the most common chronic complaints in burn survivors. Pruritus is often indistinguishable from neuropathic pain. There is a paucity of studies reporting the use of gabapentin and pregabalin to treat both pruritus and neuropathic pain. The purpose of this current study is to explore and document the effect of gabapentin and pregabalin in children and adolescent burn survivors.

Wireless micro current stimulation – an innovative electrical stimulation method for the treatment of patients with leg and diabetic foot ulcers

Clinical experience with a new electrical stimulation (ES) technique, the wireless micro current stimulation (WMCS), for the treatment of chronic wounds is described. WMCS transfers the current to any surface wound from a distance, by using oxygen's and nitrogen's ability to exchange electrons. We studied 47 patients with hard‐to‐heal wounds. Patients with venous, arterial and mixed leg ulcers were predominant; other aetiologies such as diabetic foot lesions, pressure ulcers, vasculitis and pyoderma were also included. WMCS treatment protocol specified treatment twice or thrice per week, for 45–60 minutes per session, with 1·5 μA current intensity. Standard wound care was applied to all patients, including compression bandages, if necessary. Clear progress of wound healing, even after 2 weeks, was observed in all cases. The mean reduction of the wound surface after WMCS treatment was 95% in 8 weeks. Complete healing was achieved within 3 months for the majority of the cases. No clinical side effects were observed. WMCS technology significantly accelerated wound healing for patients with hard‐to‐heal wounds of different aetiologies. This new therapy offers multiple advantages compared with the previous methods of ES, as it is contactless, free of pain and very easy to use.     

A neural model for chronic pain and pain relief by extracorporeal shock wave treatment

The paper develops a new theory of chronic pain and pain relief by extracorporeal shock wave treatment. Chronic pain without underlying anatomical disorder is looked at as a pathological control function of memory. Conditioned reflexes are considered to be engraved memory traces linking sensory input of afferent signals with motor response of efferent signals. This feature can be described by associative memory functions of the nervous system. Some conditioned reflexes may cause inappropriate or pathological reactions. Consequently, a circulus vitiosus of pain sensation and muscle and/or vessel contraction is generated when pain becomes chronic (pain spiral). The key feature is a dedicated engram responsible for a pathological (painful) reaction. The pain memory may be explained by the concept of a holographic memory model published by several authors. According to this model it is shown how nervous systems may generate and recall memory contents. The paper shows how extracorporeal shock wave treatment may reorganize pathologic memory traces, thus giving cause to real and permanent pain relief. In a generalized manner, the idea of associative memory functions may help in the understanding of conditioning as a learning process and explain extracorporeal shock wave application as an efficient treatment concept for chronic pain. This concept may open the door for new treatment approaches to chronic pain and several other disorders of the nervous system.     

Basal ganglia deep-brain stimulation for treatment of drug-resistant epilepsy: review and current data

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.     

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries

Context

Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited.

Objectives

To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI.

Method

Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments.

Results

Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant).

Conclusion

The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials.     

Therapeutic potentials of a novel method of dual-pulse gastric electrical stimulation for gastric dysrhythmia and symptoms of nausea and vomiting

BACKGROUND: The aims of this study were to investigate the effects and mechanisms of a novel method of gastric electrical stimulation on the prevention of vasopressin-induced emetic response and gastric dysrhythmias. METHODS: Fifteen dogs (10 normal, 5 vagotomized) chronically implanted with gastric serosal electrodes were used in a 3-session study (vasopressin, vasopressin plus 2-channel stimulation [DCS], and vasopressin plus dual-pulse stimulation [DPS]). RESULTS: Vasopressin induced gastric dysrhythmias and motion sickness-like symptoms (P < .05) and these effects were blocked partially with vagotomy. Both methods of DCS and DPS were capable of preventing vasopressin-induced gastric dysrhythmias (P < .05) and motion sickness-like symptoms (P < .05). The antiemetic effects of the proposed methods of DCS and DPS were abolished by vagotomy but their antidysrhythmic effects were not blocked by vagotomy. CONCLUSIONS: DCS and DPS are able to reduce vasopressin-induced gastric dysrhythmia and symptoms of nausea and vomiting. The vagal pathway is involved in the antiemetic effect but not the antidysrhythmic effect of the proposed methods of stimulation.     

Coaxial insulated bipolar electrode for monopolar and bipolar mapping of neural tissue: Technical note with emphasis on the principles of intra-operative stimulation

Summary To facilitate use of various stimulation modes for intra-operative monitoring during neurosurgical procedures, we designed and produced a variable stimulation system that consists of a coaxial bipolar flush-tip insulated stimulation electrode, and a switch box to administer monopolar or bipolar stimulation through the same stimulation electrode. The electrode is composed of components that are readily available, so that its construction can be duplicated by others at minimal expense. For mapping of neural tissue during surgical procedures, we use the monopolar stimulation mode to identify relative large areas around the site of stimulation which are free of motor nerve fibres. The bipolar stimulation mode is most useful for precise localization of motor nerve fibres and in distinguishing motor from non-motor fibres.     

The effect of high-voltage monophasic pulsed current on diabetic ulcers and their potential pathophysiologic factors: A systematic review and meta-analysis

The present review was conducted to determine the efficacy of high-voltage monophasic pulsed current (HVMPC) in treating diabetic ulcers, assess its effect on skin lesions with each of the pathophysiologic factors potentially contributing to diabetic ulcers, evaluate its safety, and identify treatment parameters. Electronic search of PubMed, Scopus, PEDro and Google Scholar databases was conducted. The revised tool for assessing risk of bias in randomised trials (RoB 2), the risk of bias in non-randomised studies-of interventions (ROBINS-I) and the Joanna Briggs Institute (JBI) critical appraisal tool were used to assess risk of bias and methodological quality. Overall quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles. Thirty-two studies matched the eligibility criteria, and included 1061 patients with 1103 skin lesions of selected aetiologies; 12 randomised controlled trials were included in quantitative synthesis. HVMPC plus standard wound care (SWC) likely increased the probability of complete wound healing of pressure ulcers (PrUs) compared with sham/no stimulation plus SWC; relative risk (RR) 2.08; 95% CI: [1.42, 3.04], p = 0.0002; I² = 0%, p = 0.61; eight studies, 358 ulcers. Although conclusive evidence regarding the effect of HVMPC on diabetic ulcers was not found, collateral evidence might suggest a potential benefit. Direct evidence, with moderate certainty, may support its efficacy in treating PrUs, albeit few adverse reactions were reported. Other observations, moreover, might indicate that this efficacy may not be limited to PrUs. Nonetheless, several aspects remain to be clarified for safe and effective application of electrical stimulation for wound healing.     

A comparative study of pelvic floor training and electrical stimulation for the treatment of genuine female stress urinary incontinence

Twenty women with pure genuine stress urinary incontinence were randomly allocated to 6 months of pelvic floor training or intravaginal electrical stimulation. The result was evaluated with a pad test and patients' rating of efficacy. Patients not cured by the first treatment given were offered the other one. A long-term follow-up was done 4 years after concluding treatment. The group of patients initially treated with pelvic floor exercises (n = 10) were significantly improved according to the pad test (P < 0.01). This corresponded very well to the subjective result, one patient being cured, five reporting insignificant symptoms, and the remaining four an improvement. The results were similar in patients allocated to intravaginal electrical stimulation (n = 10) (P < 0.05): one patient cured, four having insignificant symptoms, three improved, and two unchanged. We did not find any significant difference of results between the two groups of treatment (P < 0.10). Follow-up after 4 years in 19 patients revealed that 1 patient was further improved, 8 patients were unchanged and 5 had deteriorated. Five women were operated during the follow-up period. Pelvic floor training is an adequate method for treatment of stress urinary incontinence. Even patients with severe incontinence may show a very good result. However, a sustained effect presupposes continuing exercise and during the follow-up period of 4 years a quarter of the patients had to be operated upon to obtain permanent cure. The study also indicated that patients undergoing both treatments were further improved during the second course of treatment.     

Electrical stimulation therapy for the treatment of pressure ulcers in individuals with spinal cord injury: a systematic review and meta‐analysis

To conduct a systematic review and meta‐analysis on the effects of electrical stimulation therapy (EST) on healing pressure ulcers in individuals with spinal cord injury (SCI). CINAHL, The Cochrane Library, PubMed, SCOPUS, EMBASE, Nursing & Allied Health and Dissertation & Theses databases were searched for relevant English language articles from the date of inception to 31 January 2014. Separate searches were conducted in Google Scholar and academic journals specialised in wound care. Two reviewers independently assessed study eligibility. Studies were included if EST was used to treat pressure ulcers in individuals with SCI. A total of 599 articles were screened, and 15 studies met the inclusion criteria. A meta‐analysis with five studies demonstrated that EST significantly decreased the ulcer size by 1·32%/day [95% confidence interval (CI): 0·58–2·05, P < 0·001] compared to standard wound care (SWC) or sham EST. Another meta‐analysis conducted with four studies showed that EST increased the risk of wound healing by 1·55 times compared with standard wound care or sham EST (95% CI: 1·12 to 2·15, P < 0·0001). Because of the wide array of outcome measures across studies, a single meta‐analysis could not be conducted. EST appears to be an effective adjunctive therapy to accelerate and increase pressure ulcer closure in individuals with SCI.