OBJECTIVE: To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms.
METHODS: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life).
RESULTS: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias.
CONCLUSIONS: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.
BACKGROUND: This is an updated version of the original Cochrane Review published in 2010, Issue 9, and last updated in 2014, Issue 4. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and reduced impedance non-invasive cortical electrostimulation (RINCE).
OBJECTIVES: To evaluate the efficacy of non-invasive cortical stimulation techniques in the treatment of chronic pain.
SEARCH METHODS: For this update we searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, LILACS and clinical trials registers from July 2013 to October 2017.
SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS, RINCE and tRNS if they employed a sham stimulation control group, recruited patients over the age of 18 years with pain of three months' duration or more, and measured pain as an outcome. Outcomes of interest were pain intensity measured using visual analogue scales or numerical rating scales, disability, quality of life and adverse events.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and verified data. Where possible we entered data into meta-analyses, excluding studies judged as high risk of bias. We used the GRADE system to assess the quality of evidence for core comparisons, and created three 'Summary of findings' tables.
MAIN RESULTS: We included an additional 38 trials (involving 1225 randomised participants) in this update, making a total of 94 trials in the review (involving 2983 randomised participants). This update included a total of 42 rTMS studies, 11 CES, 36 tDCS, two RINCE and two tRNS. One study evaluated both rTMS and tDCS. We judged only four studies as low risk of bias across all key criteria. Using the GRADE criteria we judged the quality of evidence for each outcome, and for all comparisons as low or very low; in large part this was due to issues of blinding and of precision.rTMSMeta-analysis of rTMS studies versus sham for pain intensity at short-term follow-up (0 to < 1 week postintervention), (27 studies, involving 655 participants), demonstrated a small effect with heterogeneity (standardised mean difference (SMD) -0.22, 95% confidence interval (CI) -0.29 to -0.16, low-quality evidence). This equates to a 7% (95% CI 5% to 9%) reduction in pain, or a 0.40 (95% CI 0.53 to 0.32) point reduction on a 0 to 10 pain intensity scale, which does not meet the minimum clinically important difference threshold of 15% or greater. Pre-specified subgroup analyses did not find a difference between low-frequency stimulation (low-quality evidence) and rTMS applied to the prefrontal cortex compared to sham for reducing pain intensity at short-term follow-up (very low-quality evidence). High-frequency stimulation of the motor cortex in single-dose studies was associated with a small short-term reduction in pain intensity at short-term follow-up (low-quality evidence, pooled n = 249, SMD -0.38 95% CI -0.49 to -0.27). This equates to a 12% (95% CI 9% to 16%) reduction in pain, or a 0.77 (95% CI 0.55 to 0.99) point change on a 0 to 10 pain intensity scale, which does not achieve the minimum clinically important difference threshold of 15% or greater. The results from multiple-dose studies were heterogeneous and there was no evidence of an effect in this subgroup (very low-quality evidence). We did not find evidence that rTMS improved disability. Meta-analysis of studies of rTMS versus sham for quality of life (measured using the Fibromyalgia Impact Questionnaire (FIQ) at short-term follow-up demonstrated a positive effect (MD -10.80 95% CI -15.04 to -6.55, low-quality evidence).CESFor CES (five studies, 270 participants) we found no evidence of a difference between active stimulation and sham (SMD -0.24, 95% CI -0.48 to 0.01, low-quality evidence) for pain intensity. We found no evidence relating to the effectiveness of CES on disability. One study (36 participants) of CES versus sham for quality of life (measured using the FIQ) at short-term follow-up demonstrated a positive effect (MD -25.05 95% CI -37.82 to -12.28, very low-quality evidence).tDCSAnalysis of tDCS studies (27 studies, 747 participants) showed heterogeneity and a difference between active and sham stimulation (SMD -0.43 95% CI -0.63 to -0.22, very low-quality evidence) for pain intensity. This equates to a reduction of 0.82 (95% CI 0.42 to 1.2) points, or a percentage change of 17% (95% CI 9% to 25%) of the control group outcome. This point estimate meets our threshold for a minimum clinically important difference, though the lower confidence interval is substantially below that threshold. We found evidence of small study bias in the tDCS analyses. We did not find evidence that tDCS improved disability. Meta-analysis of studies of tDCS versus sham for quality of life (measured using different scales across studies) at short-term follow-up demonstrated a positive effect (SMD 0.66 95% CI 0.21 to 1.11, low-quality evidence).Adverse eventsAll forms of non-invasive brain stimulation and sham stimulation appear to be frequently associated with minor or transient side effects and there were two reported incidences of seizure, both related to the active rTMS intervention in the included studies. However many studies did not adequately report adverse events.
AUTHORS' CONCLUSIONS: There is very low-quality evidence that single doses of high-frequency rTMS of the motor cortex and tDCS may have short-term effects on chronic pain and quality of life but multiple sources of bias exist that may have influenced the observed effects. We did not find evidence that low-frequency rTMS, rTMS applied to the dorsolateral prefrontal cortex and CES are effective for reducing pain intensity in chronic pain. The broad conclusions of this review have not changed substantially for this update. There remains a need for substantially larger, rigorously designed studies, particularly of longer courses of stimulation. Future evidence may substantially impact upon the presented results.
Pain in Parkinson's disease (PD) is a debilitating symptom with a prevalence of 68%, yet is untreated 50% of the time. What is unclear, however, is which treatment is optimal for minimizing pain severity in PD. Thus, the objective of this systematic review and meta-analysis was to investigate the efficacy of a variety of novel, complimentary, and conventional treatments for pain in PD and elucidate which therapy is the most effective. A systematic search was performed using MEDLINE, PsycINFO, Embase, CINAHL, and CENTRAL databases. To identify additional articles, manual searches of reference lists of included trials were also searched. Major neurology conference proceedings occurring between January 2014 and February 2018 were also searched to identify unpublished studies that may be potentially eligible. Twenty-five randomized controlled trials that encompassed medical, surgical, and complementary therapies met our inclusion criteria and exhibited moderate quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. A conservative random-effects model was used to pool effect estimates of pain severity. The greatest reductions in pain were found with safinamide (Standardized mean difference = -4.83, 95% CI [-5.07 to -4.59], p < 0.0001), followed by cannabinoids and opioids, multidisciplinary team care, catechol-O-methyltransferase inhibitors, and electrical and Chinese therapies. Moderate effects in reducing pain were in pardoprunox and surgery, while the weakest effects were in dopaminergic agonists and miscellaneous therapies. Safinamide is an important adjunct to standard parkinsonian medication for alleviating pain in PD.
Cranial electrical stimulation (CES) is a non-invasive method of applying low-intensity electrical current to the head. It is related to but distinct from other forms of transcranial electrical stimulation including electroconvulsive therapy, transcranial direct current stimulation (tDCS), and high-definition transcranial direct current stimulation. The different versions of transcranial electrical stimulation vary in the placement of electrodes, the intensity of the current, and the waveform of the current. According to Guleyupoglu and colleagues, CES evolved from the concept of “electrosleep,” first investigated at the beginning of the 20th century. Most of the early research and applications occurred in Russia. Beginning in the 1960s, the concept of electrosleep became more popular in the USA. Because of the belief that the treatment did not actually induce sleep, but rather the sleep was a side effect of the relaxing effect of the current stimulation, the name was changed from “electrosleep” to “cranial electrical stimulation.” Other proposed names, which have not persisted, included “transcerebral electrotherapy” and “NeuroElectric Therapy.” The latter is noteworthy because it gave its name to an early CES device, the Neurotone 101, which was the first device approved by the FDA. All subsequent CES devices have been cleared for marketing by FDA based on the concept of claiming equivalency to the Neurotone 101. The status of cranial electrical stimulation devices and FDA regulation remains a matter of some controversy.
Resumen Objetivos Revisar la literatura más actual para comprobar los efectos de la fisioterapia pasiva en el tratamiento de los síntomas de la fibromialgia, diferenciando según técnicas de aplicación y valorando la efectividad según síntoma. Estrategia de búsqueda Se realiza una búsqueda bibliográfica en Medline a través de Pubmed para localizar ensayos clínicos de los últimos 5 años. Selección de estudios Se hallan 683 estudios de los que 18 son seleccionados y evaluados según la calidad metodológica con la escala PEDro. Síntesis de resultados La fisioterapia pasiva puede ser un tratamiento efectivo, ya que técnicas como la electroterapia, la liberación miofascial y la balneoterapia producen analgesia y mejoran la calidad de vida de los sujetos. La depresión mejora con la terapia manual y la balneoterapia; el sueño mejora con la TENS y la terapia manual. Conclusiones La fisioterapia pasiva puede ser un tratamiento efectivo a nivel sintomático, siendo algunas técnicas más indicadas que otras según los síntomas de mayor severidad en los pacientes. Objectives To review the most recent literature on the effects of passive physiotherapy in the treatment of fibromyalgia, including the different techniques used and the measurement of their effectiveness on each symptom. Search strategy a bibliographic search was carried out in PubMed database to locate clinical trials conducted in the previous five years. Study selection Of the 683 studies found, 18 of them were selected and assessed according to their methodological quality using the PEDro scale. Summary of results passive physiotherapy could be an effective treatment, since techniques such as electrotherapy, balneotherapy, and myofascial release improve pain and quality of life in the subjects. Depression is improved by manual therapy and balneotherapy. Transcutaneous electrical nerve stimulation (TENS) and manual therapy improve sleep. Conclusions Passive physiotherapy could be an effective symptomatic treatment. The choice of the technique must depend on the specific symptom required to be treat.
The aims of this systematic review were to study the analgesic effect of real acupuncture and to explore whether sham acupuncture (SA) type is related to the estimated effect of real acupuncture for musculoskeletal pain. Five databases were searched. The outcome was pain or disability immediately (≤1 week) following an intervention. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. Meta-regression was used to explore possible sources of heterogeneity. Sixty-three studies (6382 individuals) were included. Eight condition types were included. The pooled effect size was moderate for pain relief (59 trials, 4980 individuals, SMD -0.61, 95% CI -0.76 to -0.47; P < 0.001) and large for disability improvement (31 trials, 4876 individuals, -0.77, -1.05 to -0.49; P < 0.001). In a univariate meta-regression model, sham needle location and/or depth could explain most or all heterogeneities for some conditions (e.g., shoulder pain, low back pain, osteoarthritis, myofascial pain, and fibromyalgia); however, the interactions between subgroups via these covariates were not significant (P < 0.05). Our review provided low-quality evidence that real acupuncture has a moderate effect (approximate 12-point reduction on the 100-mm visual analogue scale) on musculoskeletal pain. SA type did not appear to be related to the estimated effect of real acupuncture.
BACKGROUND: Neuropathic pain is thought to arise from damage to the somatosensory nervous system. Its prevalence is increasing in line with many chronic disorders such as diabetes. All treatments have limited effectiveness. Given the evidence regarding psychological treatment for distress and disability in people with various chronic pain conditions, we were interested to investigate whether psychological treatments have any effects for those with chronic neuropathic pain.
OBJECTIVES: To assess the effects of psychological treatments on pain experience, disability, mood, and health-care use in adults with chronic neuropathic pain.
SEARCH METHODS: We searched for randomised controlled trials (RCTs) published in any language in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, from database inception to March 2015.
SELECTION CRITERIA: Full publications of RCTs on psychological interventions for neuropathic pain. Trials had to have lasted at least three months, had at least 20 participants in each arm at the end of treatment, and compared a psychological intervention with any active or inactive intervention.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS: Two small studies (enrolling a total of 105 participants) met the inclusion criteria. One was a standard cognitive behavioural treatment (CBT) programme for 61 people with pain from spinal cord injury, followed up for three months, and compared with a waiting list. The other was weekly group psychotherapy for 44 people with burning mouth syndrome, compared with a daily placebo tablet. The overall risk of bias was high in both trials.The CBT study assessed participants for pain, disability, mood, and quality of life, with improvement in treatment and control groups. However, there was no more improvement in the treatment group than in the control for any outcome, either post-treatment or at follow-up. The group psychotherapy study only assessed pain, classifying participants by pain severity. There is a lack of evidence on the efficacy and safety of psychological interventions for people with neuropathic pain.
AUTHORS' CONCLUSIONS: There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups.
OBJECTIVES: To conduct a systematic review and meta-analysis to examine the effect of transcranial direct current stimulation (tDCS) on reducing neuropathic pain intensity in individuals with spinal cord injury (SCI).
METHODS: Medline, CINAHL, EMBASE and PsycINFO databases were searched for all relevant articles published from 1980 to November 2014. Trials were included if (i) tDCS intervention group and a placebo control group were present; (ii) at least 50% of participants in the study had an SCI and there were at least three participants; (iii) participants were aged 18 years or older; and (iv) persistent pain for at least 3 months. Studies were excluded if: (i) the tDCS intervention group was compared with an active treatment group; (ii) there was insufficient reporting detail to enable pooling of data; and (iii) it was a nonclinical trial (that is, reviews, epidemiology, basic sciences). A standardized mean difference (SMD)±s.e. and 95% confidence interval (CI) was calculated for each outcome of interest and the results were pooled using a fixed or random effects model, as appropriate. Effect sizes were interpreted as: small >0.2, moderate >0.5, large >0.8.
RESULTS: Five studies met inclusion criteria of which four were randomized controlled trials and one was a prospective controlled trial. The pooled analysis found a significant effect of tDCS on reducing neuropathic pain after SCI post treatment (SMD=0.510±0.202; 95% CI, 0.114-0.906; P<0.012); however, this effect was not maintained at follow-up (SMD=0.353±0.272; 95% CI, -0.179 to 0.886; P<0.194). A reduction of 1.33 units on a 10-item scale was observed post treatment. No significant adverse events were reported.
CONCLUSION: Meta-analytic results indicate a moderate effect of tDCS in reducing neuropathic pain among individuals with SCI; however, the effect was not maintained at follow-up. A mean pooled decrease of 1.33 units on a 10-item scale was found post treatment. Several factors were implicated in the effectiveness of tDCS in reducing pain. Due to the limited number of studies and lack of follow-up, more evidence is required before treatment recommendations can be made.
Context Over the last four decades, the focus of spinal cord injury (SCI) rehabilitation has shifted from medical management to issues that affect quality of life and community participation. Physical therapists (PTs) need to design and implement interventions that result in maximal participation to provide an individual with SCI an effective rehabilitation program. Objective The aim of this review is to assess the extent, content, and outcomes of physical therapy (PT) interventions focused on improving the participation of individuals with SCI. Methods A search was conducted in Medline, Embase, CENTRAL, CINAHL, PEDro, and PsycINFO. We included studies, of all designs, focused on improving the participation of individuals with SCI using PT interventions.The primary author and a reviewer independently selected articles for inclusion, assessed articles quality, and extracted the data. Results Five studies met the inclusion criteria. The interventions applied were 9- and 12-month body weight-supported treadmill training in two studies, a supervised 9-month exercise program, a 12-week home exercise program, and a 10-week multidisciplinary cognitive behavioral program for coping with chronic neuropathic pain. Four of five PT interventions positively impacted the individual's perceived participation and satisfaction with participation. Conclusion The body of research by PTs on interventions to improve participation is limited. PTs must document the effects of interventions with a valid outcome tool to enable more research that examines participation. Expanding participation research will allow PTs to meet the needs of individuals with SCI and identify what interventions best facilitate integration into the community.
BACKGROUND: Chronic neuropathic pain is one of the most common and disabling symptoms in individuals with spinal cord injury (SCI). Over two-thirds of subjects with SCI suffer from chronic pain influencing quality of life, rehabilitation, and recovery. Given the refractoriness of chronic pain to most pharmacological treatments, the majority of individuals with SCI report worsening of this condition over time. Moreover, only 4-6% of patients in this cohort report improvement. Novel treatments targeting mechanisms associated with pain-maladaptive plasticity, such as electromagnetic neural stimulation, may be desirable to improve outcomes. To date, few, small clinical trials have assessed the effects of invasive and noninvasive nervous system stimulation on pain after SCI.
OBJECTIVE: We aimed to review initial efficacy, safety and potential predictors of response by assessing the effects of neural stimulation techniques to treat SCI pain.
SEARCH STRATEGY: A literature search was performed using the PubMed database including studies using the following targeted stimulation strategies: transcranial Direct Current Stimulation (tDCS), High Definition tDCS (HD-tDCS), repetitive Transcranial Magnetical Stimulation (rTMS), Cranial Electrotherapy Stimulation (CES), Transcutaneous Electrical Nerve Stimulation (TENS), Spinal Cord Stimulation (SCS) and Motor Cortex Stimulation (MCS), published prior to June of 2012. We included studies from 1998 to 2012.
RESULTS: Eight clinical trials and one naturalistic observational study (nine studies in total) met the inclusion criteria. Among the clinical trials, three studies assessed the effects of tDCS, two of CES, two of rTMS and one of TENS. The naturalistic study investigated the analgesic effects of SCS. No clinical trials for epidural motor cortex stimulation (MCS) or HD-tDCS were found. Parameters of stimulation and also clinical characteristics varied significantly across studies. Three out of eight studies showed larger effects sizes (0.73, 0.88 and 1.86 respectively) for pain reduction. Classical neuropathic pain symptoms such as dysesthesia (defined as an unpleasant burning sensation in response to touch), allodynia (pain due to a non-painful stimulus), pain in paroxysms, location of SCI in thoracic and lumbar segments and pain in the lower limbs seem to be associated with a positive response to neural stimulation. No significant adverse effects were reported in these studies.
CONCLUSIONS: Chronic pain in SCI is disabling and resistant to common pharmacologic approaches. Electrical and magnetic neural stimulation techniques have been developed to offer a potential tool in the management of these patients. Although some of these techniques are associated with large standardized mean differences to reduce pain, we found an important variability in these results across studies. There is a clear need for the development of methods to decrease treatment variability and increase response to neural stimulation for pain treatment. We discuss potential methods such as neuroimaging or EEG-guided neural stimulation and the development of better surrogate markers of response such as TMS-indexed cortical plasticity.
To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms.
METHODS:
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life).
RESULTS:
Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias.
CONCLUSIONS:
Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.
