Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults
Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non‐pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn.
To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults.
We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies.
We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults.
Data collection and analysis
Two review authors independently screened all database search results and identified papers requiring full‐text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE.
We included 15 studies with 724 participants. We found a range of treatment protocols in terms of duration of care, TENS application times and intensity of application. Briefly, duration of care ranged from four days through to three months. Similarly, we found variation of TENS application times; from 15 minutes up to hourly sessions applied four times daily. We typically found intensity of TENS set to comfortable perceptible tingling with very few studies titrating the dose to maintain this perception. Of the comparisons, we had planned to explore, we were only able to undertake a quantitative synthesis for TENS versus sham TENS. Insufficient data and large diversity in the control conditions prevented us from undertaking a quantitative synthesis for the remaining comparisons.
For TENS compared to sham TENS, five studies were suitable for pooled analysis. We described the remainder of the studies in narrative form. Overall, we judged 11 studies at high risk of bias, and four at unclear risk. Due to the small number of eligible studies, the high levels of risk of bias across the studies and small sample sizes, we rated the quality of the evidence as very low for the pooled analysis and very low individual GRADE rating of outcomes from single studies. For the individual studies discussed in narrative form, the methodological limitations, quality of reporting and heterogeneous nature of interventions compared did not allow for reliable overall estimates of the effect of TENS.
Five studies (across various neuropathic conditions) were suitable for pooled analysis of TENS versus sham TENS investigating pain intensity using a visual analogue scale. We found a mean postintervention difference in effect size favouring TENS of ‐1.58 (95% confidence interval (CI) ‐2.08 to ‐1.09, P < 0.00001, n = 207, six comparisons from five studies) (very low quality evidence). There was no significant heterogeneity in this analysis. While this exceeded our prespecified minimally important difference for pain outcomes, we assessed the quality of evidence as very low meaning we have very little confidence in this effect estimate and the true effect is likely to be substantially different from that reported in this review. Only one study of these five investigated health related quality of life as an outcome meaning we were unable to report on this outcome in this comparison. Similarly, we were unable to report on global impression of change or changes in analgesic use in this pooled analysis.
Ten small studies compared TENS to some form of usual care. However, there was great diversity in what constituted usual care, precluding pooling of data. Most of these studies found either no difference in pain outcomes between TENS versus other active treatments or favoured the comparator intervention (very low quality evidence). We were unable to report on other primary and secondary outcomes in these single trials (health‐related quality of life, global impression of change and changes in analgesic use).
Of the 15 included studies, three reported adverse events which were minor and limited to 'skin irritation' at or around the site of electrode placement (very low quality evidence). Three studies reported no adverse events while the remainder did not report any detail with regard adverse events.
In this review, we reported on the comparison between TENS and sham TENS. The quality of the evidence was very low meaning we were unable to confidently state whether TENS is effective for pain control in people with neuropathic pain. The very low quality of evidence means we have very limited confidence in the effect estimate reported; the true effect is likely to be substantially different. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment modality.
William Gibson, Benedict M Wand, Neil E O'Connell
Plain language summary
Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain
For adults with neuropathic pain, it is impossible to confidently state whether TENS is effective in relieving pain when compared to sham TENS.
Neuropathic pain is pain due to injury or disease to nerves and can be difficult to treat effectively. It may occur following direct nerve injury or develop due to problems like diabetes, shingles and carpal tunnel syndrome. TENS is a common treatment for a range of pain conditions. It involves using a small battery operated unit to apply low level electrical currents through electrodes attached to the skin. This is suggested to relieve pain.
Does TENS improve pain intensity and health related quality of life in adults with neuropathic pain?
We reviewed all eligible clinical trials comparing TENS to 'fake' TENS (known as 'sham'), usual care or no treatment, or comparing TENS plus usual care versus usual care alone, for neuropathic pain in adults. As of September 2016, we found 15 studies eligible for inclusion. Of these 15 studies, we were able to combine results from five studies to investigate the effect of TENS compared to sham TENS for treatment of pain. The studies involved a range of neuropathic pain problems (e.g. people with spinal cord injury, back pain with nerve involvement, complications associated with diabetes, etc.). We found the quality of the studies overall to be low.
We were unable to confidently state whether TENS is effective in relieving pain compared to sham TENS in people with neuropathic pain. This is due to the very low quality of the evidence, which means we have very limited confidence in this result and that future studies are likely to change this result. Lack of reported data meant we were unable to draw any conclusion on the effect of TENS treatment on health related quality of life, pain relieving medicine use or people's impression of how TENS changed their condition.
We described the results of 10 further studies comparing TENS against other types of treatment. These 10 studies were quite varied and so we could not combine them and analyse them together. This, together with the very low quality of these 10 studies, meant we were unable to judge pain relief, health related quality of life, pain medication use or impression of change.
In three of the 15 studies, some people using TENS experienced skin irritation under the electrode pads. Three studies reported no problems and the remaining studies did not provide any details on side effects. Based on this, it is not realistic to comment on side effects associated with TENS use.
William Gibson, Benedict M Wand, Neil E O'Connell
Implications for practice
For people with neuropathic pain
This review presents very low quality evidence and cannot confidently state whether transcutaneous electrical nerve stimulation (TENS) is effective for pain relief compared to sham TENS in people with neuropathic pain. We have very limited confidence in this estimate of effect given the identified quality issues in the published evidence. People with neuropathic pain should bear in mind the low number of studies, the low quality of this evidence and the fact that the true effect is very likely to be different from that reported here when considering whether or not to use TENS for pain. We are unable to make any judgement on the effect of TENS on health related quality of life, global impression of change or medication use. Some studies reported minor skin irritation with TENS while others reported no adverse events. The majority did not report adverse events and we are, therefore, unable to make meaningful comment on TENS and associated adverse events.
This review is unable to state the effect of TENS versus sham TENS for pain relief due to the very low quality of the included evidence. The low number and small size of included studies and very low quality of the evidence means this result should be viewed with very limited confidence and the true effect is very likely different from that reported here. A small number of studies reported only minor adverse events (skin irritation). The majority of studies did not provide any detail on the safety profile of TENS; this should be explicitly addressed in future studies.
For policy makers and funders
This review neither refutes nor supports the use of TENS in management of neuropathic pain. The results reported here reflect short‐term outcome assessment only, are derived from studies that have substantial methodological limitations and may not be reflective of how TENS is typically used by people with pain.
Implications for research
TENS is a portable, easily administered modality which is accessed and used by people with pain as required. It is recommended that future studies reflect this (i.e. TENS should be self‐administered by the person and investigated in this manner). Blinding in physical interventions such as TENS is challenging. If sham TENS studies are used, at the least the sham TENS devices should be identical and appear 'active' in an effort to maintain the perception of treatment validity. Efforts should be made to preserve the naivety of the participant to the intervention and treatment providers/assessors should be blinded to group allocation. Studies in which participants self‐administer the intervention would be very helpful in improving this aspect of future TENS research. Consideration may be given to further studies assessing optimal care versus optimal care plus active TENS as an acknowledgment that sham TENS methodologies may be inherently flawed.
Improved quality in study design and reporting would significantly add to the confidence in our estimates of effectiveness. Future studies should consider the IMMPACT recommendations for the design of studies in chronic pain to ensure that outcomes, thresholds for clinical importance and study designs are optimal (Dworkin 2008; Dworkin 2009; Dworkin 2010; Turk 2008). Clear guidance on study design is provided by the CONSORT statement and subsequent checklist (Schulz 2010). Integral to this should be the requirement for clearly defined neuropathic pain participants with suitable diagnostic criteria required for inclusion. Interventions should be clearly described and we recommend active TENS treatments should be of sufficient intensity to be perceived as 'strong' with participants titrating intensity to maintain this perception throughout the duration of treatment (Johnson 2011; Moran 2011; Sluka 2013). A recurring feature across reporting of studies in this field was lack of published outcome data. We would strongly recommend all primary specified outcomes be reported in summary form for all comparison groups (mean/median and standard deviation/range/interquartile ranges) at baseline and all assessment times post‐randomisation. This would greatly aid future assessment of effect via systematic review of studies.
With regard to pain intensity outcome assessment, this review highlights discrepancy in both the nature of the parameter assessed (mean weekly pain, current pain, etc.) and the timing of assessment. Given that TENS is suggested to have both rapid onset and offset of effect (Moran 2011), we would propose that assessment of effect on pain should ideally be assessed during TENS application at each prespecified assessment time with possibly at that time an additional weekly or 24 hour mean measure to assess longer term effects. Possible pain reducing effect of TENS may allow changes in function and self‐efficacy which in turn may influence overall longer term perception of pain. It should be noted though that the relationship between efficacy of interventions on pain and disability in people with chronic pain is likely complex and not predictable (Saragiotto 2017). Valid measures of function/quality of life should also be key reportable outcome measures along with pain intensity in future TENS studies.