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.
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.
BACKGROUND: Chronic pain is frequent in persons living with spinal cord injury (SCI). Conventionally, the pain is treated pharmacologically, yet long-term pain medication is often refractory and associated with side effects. Non-pharmacological interventions are frequently advocated, although the benefit and harm profiles of these treatments are not well established, in part because of methodological weaknesses of available studies.
OBJECTIVES: To critically appraise and synthesise available research evidence on the effects of non-pharmacological interventions for the treatment of chronic neuropathic and nociceptive pain in people living with SCI.
SEARCH METHODS: The search was run on the 1st March 2011. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), four other databases and clinical trials registers. In addition, we manually searched the proceedings of three major scientific conferences on SCI. We updated this search in November 2014 but these results have not yet been incorporated.
SELECTION CRITERIA: Randomised controlled trials of any intervention not involving intake of medication or other active substances to treat chronic pain in people with SCI.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in the included studies. The primary outcome was any measure of pain intensity or pain relief. Secondary outcomes included adverse events, anxiety, depression and quality of life. When possible, meta-analyses were performed to calculate standardised mean differences for each type of intervention.
MAIN RESULTS: We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self-hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review.
For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11-point visual analogue scale (VAS) (0-10) was a reduction of -1.90 units (95% confidence interval (CI) -3.48 to -0.33; P value 0.02) in the short term and of -1.87 (95% CI -3.30 to -0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of -1.9 score points for the Short Form (SF)-36 item for pain experience (95% CI -3.4 to -0.4; P value 0.01) and -2.8 pain VAS units (95% CI -3.77 to -1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self-hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long-lasting side effects of the interventions.
AUTHORS' CONCLUSIONS: Evidence is insufficient to suggest that non-pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non-pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology.
BACKGROUND: Neuropathic pain has various physiologic and psychosocial aspects. Hence, there is a growing use of adjunct nonpharmacological therapy with traditional pharmacotherapy to reduce neuropathic pain post spinal cord injury (SCI). OBJECTIVE: The purpose of this study was to conduct a systematic review of published research on nonpharmacological treatment of neuropathic pain after SCI. METHODS: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing nonpharmacological treatment of pain post SCI. Articles were restricted to the English language. Article selection was conducted by 2 independent reviewers with the following inclusion criteria: the subjects participated in a treatment or intervention for neuropathic pain; at least 50% of the subjects had an SCI; at least 3 subjects had an SCI; and a definable intervention was being studied. Data extracted included study design, study type, subject demographics, inclusion and exclusion criteria, sample size, outcome measures, and study results. Randomized controlled trials (RCTs) were assessed for quality using the Physiotherapy Evidence Database (PEDro) assessment scale. Levels of evidence were assigned to each intervention using a modified Sackett scale. RESULTS: The 16 articles selected for this review fell into 1 of 2 categories of nonpharmacological management of pain after SCI; physical and behavioral treatments. The pooled sample size of all studies included 433 participants. Of the 16 studies included, 7 were level 1, 3 were level 2, and 6 were level 4 studies. CONCLUSIONS: Physical interventions demonstrated the strongest evidence based on quality of studies and numbers of RCTs in the nonpharmacological treatment of post-SCI pain. Of these interventions, transcranial electrical stimulation had the strongest evidence of reducing pain. Despite a growing body of literature, there is still a significant lack of research on the use of nonpharmacological therapies for SCI pain.
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.
Systematic Review Question»Systematic review of interventions
