Characterising the Features of 381 Clinical Studies Evaluating Transcutaneous Electrical Nerve Stimulation (TENS) for Pain Relief: A Secondary Analysis of the Meta-TENS Study to Improve Future Research.

Background and Objectives: Characterising the features of methodologies, clinical attributes and intervention protocols, of studies is valuable to advise directions for research and practice. This article reports the findings of a secondary analysis of the features from studies screened as part of a large systematic review of TENS (the meta-TENS study). Materials and Methods: A descriptive analysis was performed on information associated with methodology, sample populations and intervention protocols from 381 randomised controlled trials (24,532 participants) evaluating TENS delivered at a strong comfortable intensity at the painful site in adults with pain, irrespective of diagnosis. Results: Studies were conducted in 43 countries commonly using parallel group design (n = 334) and one comparator group (n = 231). Mean ± standard deviation (SD) study sample size (64.05 ± 58.29 participants) and TENS group size (27.67 ± 21.90 participants) were small, with only 13 of 381 studies having 100 participants or more in the TENS group. Most TENS interventions were 'high frequency' (>10 pps, n = 276) and using 100 Hz (109/353 reports that stated a pulse frequency value). Of 476 comparator groups, 54.2% were active treatments (i.e., analgesic medication(s), exercise, manual therapies and electrophysical agents). Of 202 placebo comparator groups, 155 used a TENS device that did not deliver currents. At least 216 of 383 study groups were able to access other treatments whilst receiving TENS. Only 136 out of 381 reports included a statement about adverse events. Conclusions: Clinical studies on TENS are dominated by small parallel group evaluations of high frequency TENS that are often contaminated by concurrent treatment(s). Study reports tended focus on physiological and clinical implications rather than the veracity of methodology and findings. Previously published criteria for designing and reporting TENS studies were neglected and this should be corrected in future research using insights gleaned from this analysis.

Efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: a systematic review and meta-analysis of 381 studies (the meta-TENS study).

OBJECTIVE: To investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for relief of pain in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane Central, Embase (and others) from inception to July 2019 and updated on 17 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials (RCTs) comparing strong non-painful TENS at or close to the site of pain versus placebo or other treatments in adults with pain, irrespective of diagnosis. DATA EXTRACTION AND SYNTHESIS: Reviewers independently screened, extracted data and assessed risk of bias (RoB, Cochrane tool) and certainty of evidence (Grading and Recommendations, Assessment, Development and Evaluation). Mean pain intensity and proportions of participants achieving reductions of pain intensity (≥30% or >50%) during or immediately after TENS. Random effect models were used to calculate standardised mean differences (SMD) and risk ratios. Subgroup analyses were related to trial methodology and characteristics of pain. RESULTS: The review included 381 RCTs (24 532 participants). Pain intensity was lower during or immediately after TENS compared with placebo (91 RCTs, 92 samples, n=4841, SMD=-0·96 (95% CI -1·14 to -0·78), moderate-certainty evidence). Methodological (eg, RoB, sample size) and pain characteristics (eg, acute vs chronic, diagnosis) did not modify the effect. Pain intensity was lower during or immediately after TENS compared with pharmacological and non-pharmacological treatments used as part of standard of care (61 RCTs, 61 samples, n=3155, SMD = -0·72 (95% CI -0·95 to -0·50], low-certainty evidence). Levels of evidence were downgraded because of small-sized trials contributing to imprecision in magnitude estimates. Data were limited for other outcomes including adverse events which were poorly reported, generally mild and not different to comparators. CONCLUSION: There was moderate-certainty evidence that pain intensity is lower during or immediately after TENS compared with placebo and without serious adverse events. PROSPERO REGISTRATION NUMBER: CRD42019125054.

Does TENS Reduce the Intensity of Acute and Chronic Pain? A Comprehensive Appraisal of the Characteristics and Outcomes of 169 Reviews and 49 Meta-Analyses.

Background and Objectives: Uncertainty about the clinical efficacy of transcutaneous electric nerve stimulation (TENS) to alleviate pain spans half a century. There has been no attempt to synthesise the entire body of systematic review evidence. The aim of this comprehensive review was to critically appraise the characteristics and outcomes of systematic reviews evaluating the clinical efficacy of TENS for any type of acute and chronic pain in adults. Materials and Methods: We searched electronic databases for full reports of systematic reviews of studies, overviews of systematic reviews, and hybrid reviews that evaluated the efficacy of TENS for any type of clinical pain in adults. We screened reports against eligibility criteria and extracted data related to the characteristics and outcomes of the review, including effect size estimates. We conducted a descriptive analysis of extracted data. Results: We included 169 reviews consisting of eight overviews, seven hybrid reviews and 154 systematic reviews with 49 meta-analyses. A tally of authors' conclusions found a tendency toward benefits from TENS in 69/169 reviews, no benefits in 13/169 reviews, and inconclusive evidence in 87/169 reviews. Only three meta-analyses pooled sufficient data to have confidence in the effect size estimate (i.e., pooled analysis of >500 events). Lower pain intensity was found during TENS compared with control for chronic musculoskeletal pain and labour pain, and lower analgesic consumption was found post-surgery during TENS. The appraisal revealed repeated shortcomings in RCTs that have hindered confident judgements about efficacy, resulting in stagnation of evidence. Conclusions: Our appraisal reveals examples of meta-analyses with 'sufficient data' demonstrating benefit. There were no examples of meta-analyses with 'sufficient data' demonstrating no benefit. Therefore, we recommend that TENS should be considered as a treatment option. The considerable quantity of reviews with 'insufficient data' and meaningless findings have clouded the issue of efficacy. We offer solutions to these issues going forward.

Protocols for inducing homeostatic plasticity reflected in the corticospinal excitability in healthy human participants: A systematic review and meta-analysis.

Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non-invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta-analysis was to investigate the effect of homeostatic plasticity induction protocols on motor evoked potentials (MEP) in healthy participants. Four databases were searched (Medline, Scopus, Embase and Cochrane library). Studies describing the application of two blocks of NIBS of the primary motor cortex with an interval of no stimulation between blocks reporting changes in corticospinal excitability by MEP amplitude were included. Thirty-seven reports with 55 experiments (700 participants) were included. Study quality was considered poor overall, with heterogeneity in study size, sample and designs. Two blocks of excitatory stimulation at the primary motor cortex produced a homeostatic response (decreased MEP) between 0 and 30 min post-protocols, when compared with a single stimulation block. Two blocks of inhibitory stimulation at the primary motor cortex using interval duration of 10 min or less produced a homeostatic response (increased MEP) between 0 and 30 min post-protocols, when compared with a single stimulation block. There were no differences in MEPs when compared with baseline MEPs. In conclusion, homeostatic plasticity induction using two blocks of NIBS with an interval of 10 min or less without stimulation between blocks produces a homeostatic response up to 30 min post-protocol. Improvements in participant selection, sample sizes and protocols of NIBS techniques are needed.

Is Transcranial Direct Current Stimulation (tDCS) Effective for the Treatment of Pain in Fibromyalgia? A Systematic Review and Meta-Analysis.

BACKGROUND: Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment. OBJECTIVE: To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia. METHODS: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals. RESULTS: Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made. CONCLUSIONS: tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies. PERSPECTIVE: This systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.

The effect of interactive virtual reality on pain perception: a systematic review of clinical studies.

Purpose: The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical pain condition.Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane library and Web of Science. Two reviewers screened reports and extracted the data. A third reviewer acted as an arbiter. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and uncontrolled trials. Crossover and parallel-group designs were included. Risk of bias was assessed for all included studies.Results: Thirteen clinical studies were included. The majority of studies investigated a sample of participants with chronic pain. Six were controlled trials and seven uncontrolled studies. Findings from controlled research suggest that interactive virtual reality may reduce pain associated with ankylosing spondylitis and post-mastectomy, but results are inconsistent for patients with neck pain. Findings from uncontrolled studies suggest that interactive virtual reality may reduce neuropathic limb pain, and phantom limb pain, but had no effect on nonspecific chronic back pain.Conclusions: There is a need for more rigorous randomized control trials in order to conclude on the effectiveness of the use of virtual reality for the management of pain.Implications for rehabilitationInteractive virtual reality has been increasingly used in the rehabilitation of painful conditions.Interactive virtual reality using exergames may promote distraction from painful exercises and reduce pain post-mastectomy and in patients with ankylosing spondylitis.Interactive virtual representation of limbs may reduce neuropathic and phantom limb pain.

The clinical efficacy of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain: a protocol for a meta-analysis of randomised controlled trials (RCTs).

INTRODUCTION: The aim of this systematic review with meta-analysis is to evaluate the clinical efficacy of transcutaneous electrical nerve stimulation (TENS) for any type of acute and chronic pain in adults. METHODS AND ANALYSIS: We intend to search electronic databases (Cochrane Library, MEDLINE, Embase, CINAHL, PsycINFO, LILACS, PEDRO, Web of Science, AMED and SPORTDiscus) from inception to the present day to identify all randomised controlled trials (RCT) on the use of TENS in adults for any type of pain including acute pain, chronic pain and cancer-related pain. We will screen the RCTs against eligibility criteria for inclusion in our review. Two reviewers will independently undertake RCT selection, data extraction and risk of bias assessment. Primary outcomes will be: (i) participant-reported pain relief of ≥30% expressed as frequency (dichotomous) data; and (ii) participant-reported pain intensity expressed as mean (continuous) data. We will conduct meta-analyses to determine risk ratio for dichotomous data, and mean difference (MD) or standardised MD for continuous data for TENS versus placebo TENS, no treatment or waiting list control, standard of care, and other treatments. Subgroup analyses will include different pain conditions (eg, acute vs chronic), TENS intensity, during versus after TENS, TENS as a sole treatment versus TENS in combination with other treatments and TENS administered as a single dose versus repetitive dose. ETHICS AND DISSEMINATION: This systematic review will not use data from individual participants, and the results will be disseminated in a peer-reviewed publication and presented at a conference. PROSPERO REGISTRATION NUMBER: CRD42019125054.

Managing limb pain using virtual reality: a systematic review of clinical and experimental studies.

Purpose: The aim of this systematic review was to assess the effect of virtual representation of body parts on pain perception in patients with pain and in pain-free participants exposed to experimentally induced pain.Methods: Databases searched: Medline, PsycInfo, CINAHL, and Web of Science. Studies investigating participants with clinical pain or those who were pain free and exposed to experimentally induced pain were analysed separately.Results: Eighteen clinical studies and seven experimental studies were included. Randomised controlled clinical trials showed no significant difference between intervention and control groups for pain intensity. Clinical studies with a single group pretest-posttest design showed a reduction in pain after intervention. In the studies including a sample of pain free participants exposed to experimentally induced pain there was an increase in pain threshold when the virtual arm was collocated with the real arm, when it moved in synchrony with the real arm, and when the colour of the stimulated part of the virtual arm became blue. Observing a virtual arm covered with iron armour reduced pain.Conclusions: The use of virtual representations of body parts to reduce pain is promising. However, due to the poor methodological quality and limitations of primary studies, we could not find conclusive evidence.Implications for rehabilitationVirtual reality has been increasingly used in the rehabilitation of painful and dysfunctional limbs.Virtual reality can be used to distract attention away from acute pain and may also provide corrective psychological and physiological environments.Virtual representation of body parts has been used to provide a corrective re-embodiment of painful dysmorphic body parts, and primary research shows promising results.

Mirror therapy: A potential intervention for pain management

Summary The consequences of chronic pain and associated disabilities to the patient and to the health care system are well known. Medication is often the first treatment of choice for chronic pain, although side effects and high costs restrict long-term use. Inexpensive, safe and easy to self-administer non-pharmacological therapies, such as mirror therapy, are recommended as adjuncts to pain treatment. The purpose of this review is to describe the principles of use of mirror therapy so it can be incorporated into a health care delivery. The physiological rationale of mirror therapy for the management of pain and the evidence of clinical efficacy based on recent systematic reviews are also discussed. Mirror therapy, whereby a mirror is placed in a position so that the patient can view a reflection of a body part, has been used to treat phantom limb pain, complex regional pain syndrome, neuropathy and low back pain. Research evidence suggests that a course of treatment (four weeks) of mirror therapy may reduce chronic pain. Contraindications and side effects are few. The mechanism of action of mirror therapy remains uncertain, with reintegration of motor and sensory systems, restored body image and control over fear-avoidance likely to influence outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy for the patient to self-administer.

Changing the size of a mirror-reflected hand moderates the experience of embodiment but not proprioceptive drift: a repeated measures study on healthy human participants.

Mirror visual feedback is used for reducing pain and visually distorting the size of the reflection may improve efficacy. The findings of studies investigating size distortion are inconsistent. The influence of the size of the reflected hand on embodiment of the mirror reflection is not known. The aim of this study was to compare the effect of magnifying and minifying mirror reflections of the hand on embodiment measured using an eight-item questionnaire and on proprioceptive drift. During the experiment, participants (n = 45) placed their right hand behind a mirror and their left hand in front of a mirror. Participants watched a normal-sized, a magnified and a minified reflection of the left hand while performing synchronised finger movements for 3 min (adaptive phase). Measurements of embodiment were taken before (pre) and after (post) synchronous movements of the fingers of both hands (embodiment adaptive phase). Results revealed larger proprioceptive drift post-adaptive phase (p = 0.001). Participants agreed more strongly with questionnaire items associated with location, ownership and agency of the reflection of the hand post-adaptive phase (p < 0.001) and when looking at the normal-sized reflection (p < 0.001). In conclusion, irrespective of size, watching a reflection of the hand while performing synchronised movements enhances the embodiment of the reflection of the hand. Magnifying and minifying the reflection of the hand has little effect on proprioceptive drift, but it weakens the subjective embodiment experience. Such factors need to be taken into account in future studies using this technique, particularly when assessing mirror visual feedback for pain management.

Mirror therapy: A potential intervention for pain management.

The consequences of chronic pain and associated disabilities to the patient and to the health care system are well known. Medication is often the first treatment of choice for chronic pain, although side effects and high costs restrict long-term use. Inexpensive, safe and easy to self-administer non-pharmacological therapies, such as mirror therapy, are recommended as adjuncts to pain treatment. The purpose of this review is to describe the principles of use of mirror therapy so it can be incorporated into a health care delivery. The physiological rationale of mirror therapy for the management of pain and the evidence of clinical efficacy based on recent systematic reviews are also discussed. Mirror therapy, whereby a mirror is placed in a position so that the patient can view a reflection of a body part, has been used to treat phantom limb pain, complex regional pain syndrome, neuropathy and low back pain. Research evidence suggests that a course of treatment (four weeks) of mirror therapy may reduce chronic pain. Contraindications and side effects are few. The mechanism of action of mirror therapy remains uncertain, with reintegration of motor and sensory systems, restored body image and control over fear-avoidance likely to influence outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy for the patient to self-administer.