Summary of main results

We reviewed and critically appraised research evidence on the effectiveness and safety of non‐pharmacological interventions for the treatment of chronic pain in people living with SCI. We identified 16 randomised trials with a total of 616 participants with SCI and a variety of non‐pharmacological treatment approaches. Given the multiple methodological problems of these studies, an overall conclusion about their effectiveness and safety is not possible.

Transcranial direct current stimulation (tDCS) was superior to a sham intervention when the estimates of two studies were combined. However, overall evidence for the effectiveness of tDCS in reducing chronic pain in SCI was scarce and inconclusive. Data available from randomised studies on repetitive transcranial magnetic stimulation (rTMS) did not support its effectiveness in reducing chronic pain in persons living with SCI. One study including several related experiments suggested its effectiveness in a mixed study population but not in the SCI subgroup (Lefaucheur 2007). A second study (Defrin 2007) did not find a beneficial effect of active rTMS over a sham intervention, and a third study (Kang 2009) was inconclusive with regard to pain reduction.

Two studies on cranial electrotherapy stimulation (CES) had methodological weaknesses including high risk of selective reporting (Capel 2003) and baseline imbalance (Tan 2011), and a third study (Tan 2006) was inconclusive with regard to pain reduction.

Three trials reported a beneficial effect of an exercise programme on chronic pain (Mulroy 2011; Curtis 1999; Hicks 2003), but all had methodological shortcomings including lack of blinding and proper randomisation. In addition, the use of 'no treatment' or wait list control interventions in pain studies is problematic because it might yield different pain outcomes even when compared with placebo interventions (Hróbjartsson 2010).

In two trials acupuncture was not superior to sham acupuncture or Trager treatment in reducing pain (Dyson‐Hudson 2001; Dyson‐Hudson 2007).

Self‐hypnosis was compared with EMG biofeedback in one trial (Jensen 2009). Although the study authors concluded that both interventions decreased pain, the data are difficult to interpret as no sham control group was included and significant imbalance in baseline pain scores was evident between groups.

Only one trial focused on transcutaneous electrical nerve stimulation (TENS) (Doctor 1996). Results of this study suggest that treatment expectations and type of pain (neuropathic or musculoskeletal) are effect modifiers. However, available data do not allow firm conclusions.

A multi‐disciplinary cognitive behavioural programme was compared with no treatment (waiting list) in one trial (Heutink 2012). Although this type of control group likely favoured the experimental intervention, it revealed no short‐term or long‐term benefits of the programme.

Overall completeness and applicability of evidence

Completeness of the evidence

Overall, each type of intervention group included only a few studies; the maximum number of separate studies included in a meta‐analysis was two. In these meta‐analyses, statistical heterogeneity was low to moderate, with I² values ranging from 0% to 55%. Both tDCS trials (Fregni 2006; Soler 2010) were included in a meta‐analysis, and upon request one study author provided additional data. Evidence on the effectiveness of rTMS, CES and exercise programmes was poor because two of three rTMS trials, two of three CES trials and all three exercise programme trials had high overall risk of bias. These studies were excluded from the sensitivity analysis. With only one trial for self‐hypnosis (Jensen 2009), one for TENS (Doctor 1996) and one for behavioural therapy (Heutink 2012), evidence for these three types of interventions was scarce and, again, was fraught with methodological problems. Two trials investigated the effects of acupuncture. However, one study compared acupuncture versus a sham intervention (Dyson‐Hudson 2007) and another versus Trager treatment (Dyson‐Hudson 2001); consequently, we refrained from pooling the data.

We initially planned to conduct subgroup analyses for trials in patients with different types of SCI or pain. However, the small number of included studies made this impossible. Further, we did not perform a planned sensitivity analysis for studies in which persons with SCI were only a subgroup because both trials with mixed populations had major methodological shortcomings related to baseline imbalance (Curtis 1999) and outcome reporting (Lefaucheur 2007). Nine of the 16 included trials provided information about the safety of the intervention or mentioned adverse effects. Thus, evidence on the safety of non‐pharmacological trials was incomplete.

Regarding representation of both sexes, the study populations of included trials reflect the adult SCI population, with about 70% of persons being male (van den Berg 2010). The mean age of the trial populations ranged from 35 to 56 years, and wide age ranges were noted in the individual studies. It is important to note that none of the trials included participants younger than 18 years of age, suggesting that non‐pharmacological treatments for chronic pain in children with SCI have not been studied in randomised trials.

Applicability

Among the range of non‐pharmacological pain treatments currently used in routine clinical practice, only some have been investigated in the included trials. TENS, physical training and acupuncture are commonly used for pain reduction (Cardenas 2006; Heutink 2011; Norrbrink 2004). When asked about pain treatments used, persons with SCI mentioned massage, heat therapy and other physiotherapy as the most commonly used treatments for chronic pain (Cardenas 2006; Norrbrink 2004; Widerstrom‐Noga 2003). Other frequently applied therapies include ice therapy, mental relaxation and range‐of‐motion training, psychological treatment and neurosurgery. We identified solely one randomised study on psychological treatment (Heutink 2012) but none on the other interventions. In particular, none of the neurosurgical interventions proposed for pain treatment have been evaluated in randomised controlled trials.

Most of the studied interventions are potentially applicable in any person with SCI pain. Nevertheless, some specific interventions have certain contraindications that limit their applicability. For instance, brain stimulation therapies are contraindicated in persons with a family or personal history of epilepsy, serious psychological or psychiatric disorders or metal implants. Acupuncture is not indicated in persons with bleeding disorders.

Quality of the evidence

For any of the eight intervention types, the maximum number of trials included in the meta‐analysis was two. All but two studies (Mulroy 2011; Tan 2011) had sample sizes of 40 or fewer participants. With more than 100 participants, the recent study by Tan 2011 illustrates that in this particular population, larger multi‐centre trials are feasible. Given that SCI is infrequent in many countries, the number of participants who are eligible for a clinical trial is low. To obtain study populations of adequate size, multi‐centre studies and larger research collaborations are crucially needed. In meta‐analyses of osteoarthritis trials with pain outcomes, it could be shown that studies with small sample size overestimated the benefit of therapeutic interventions as compared with larger studies (Nüesch 2010).

None of the included trials were considered to have low risk of bias. Twelve studies were judged as being at high risk of bias in at least one of the seven domains of the risk of bias tool of The Cochrane Collaboration and were excluded in the sensitivity analysis. The most predominant weaknesses were lack of blinding of participants and personnel and selection of potentially invalid control interventions, potentially invalidating any conclusions regarding the effectiveness of interventions. In eight trials, blinding was precluded by the nature of the study intervention or was not successful. Blinding of participants and personnel is a major challenge in RCTs. In particular with non‐pharmacological treatments, the development of adequate control interventions is challenging. One way to attempt to reduce bias involves using 'attention control groups' with similar frequency and duration of contact with health care professionals as those in the treatment group but with no active intervention. However, several included studies used only waiting list or 'no treatment' control groups. Despite randomisation, several trials were fraught with an imbalance between study groups in baseline pain scores. This was the second most common potential source of bias. In eight trials, participants had both neuropathic and non‐neuropathic pain conditions. Given that an intervention might work better or worse with one particular type of pain, the case mix may hamper correct interpretation of the outcome data. Published aggregated data did not allow stratified analyses by pain type.

We included only trials that addressed chronic pain. However, these trials included participants at different stages of chronic pain, and outcome measures were taken at different time points relative to SCI onset and time of intervention. This represents an important source of heterogeneity. The data do not allow conclusions on the optimal time point for starting chronic pain treatment after SCI.

The trials included in our review used a broad range of measures for pain, which reflects the absence of commonly accepted standards for this outcome. In the included publications, most instruments used were described as having good validity and reliability. However, the International Spinal Cord Pain Data Set (Widerstrom‐Noga 2008) and the Report of the National Institute on Disability and Rehabilitation Research Spinal Cord Injury (NIDRR SCI) Measures meeting (Bryce 2007) specifically recommended that a numerical rating scale should be used to measure pain intensity. The latter also recommended use of the SF‐36 pain item and MPI or BPI to measure pain interference (Bryce 2007). Further, the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) recommended several outcome measures for different pain domains, although these recommendations were not SCI‐specific (Dworkin 2008; IMMPACT Recommendations 2005). To date, such collaborative efforts have not led to a unified framework for studies on chronic SCI pain.

Potential biases in the review process

Our search strategy comprised extensive literature searches of several major electronic databases, trial registers and conference proceedings as well as contact with experts in the field. Despite these searches, we may have missed eligible studies, in particular if they were not published in indexed peer‐reviewed journals. Our search update yielded several potentially eligible studies (listed under Characteristics of studies awaiting classification) that will be considered in an update of this review. Because of the small number of trials identified for each of the intervention types, we refrained from performing formal statistical tests to detect reporting bias.

To provide a critical discussion of the current state of interventional research on non‐pharmacological SCI pain treatments, we chose to include studies with methodological weaknesses such as unblinded participants, waiting list controls or obvious imbalances in pain measurements at baseline. We stress that these studies are potentially biased towards and may overestimate the effectiveness of experimental treatments. We further emphasise that inclusion of a trial in this review should not be interpreted as accepting it as internally valid and trust that our own conclusions are sufficiently cautious.

In the statistical analyses of all included studies, the data derived from ordinal scales were treated as continuous outcomes and expressed as mean, standard deviation or relative change. These choices made by the trialists also determined our approach and, consequently, represent one of the methodological limitations of our review. It has been argued that ordinal scales do not have the same mathematical properties as continuous variables (Merbitz 1989), and that this may lead to incorrect inference from the data (Stucki 1996). One solution is to convert outcome data to the cardinal metric through use of the Rasch model and to perform an individual patient data meta‐analysis (Newby 2009). However, limited available aggregated data did not allow this approach in this review.

Agreements and disagreements with other studies or reviews

In 2010, the Spinal Cord Injury Rehabilitation Evidence (SCIRE) project published a review on pain treatment following spinal cord injury (SCIRE 2010), which also covered non‐pharmacological approaches and surgical interventions. Although our current review was restricted deliberately to randomised controlled trials, the SCIRE review also included non‐randomised studies (e.g. those using before‐after comparisons). This explains why, for some types of interventions, the conclusions of the SCIRE review differ from ours. In the SCIRE review, tDCS and CES trials were found to be effective. Our findings are consistent with the findings of the SCIRE project for tDCS but do not confirm the effectiveness of CES. For rTMS, the SCIRE review identified solely the trial of Defrin 2007 and concluded that repetitive transcranial magnetic stimulation reduces post‐SCI pain, in contrast to the findings of our review. For exercise programmes, the SCIRE authors made a distinction between exercise for post‐SCI pain and for shoulder pain and identified additional studies comparing baseline and post‐treatment measures (pre‐post trial). They concluded that exercise reduces both post‐SCI pain and shoulder pain, which is in line with our findings. Also for acupuncture, their conclusions were consistent with ours: Acupuncture may reduce post‐SCI pain but is no more effective than Trager treatment or sham acupuncture. Further, the SCIRE review identified a pre‐post study on hypnotic suggestion that was not included in our review. It concluded that hypnosis may reduce pain intensity post‐SCI. Based on two controlled trials, the SCIRE review concluded that cognitive behavioural pain management alone does not alter post‐SCI pain. Furthermore, SCIRE identified two non‐randomised trials on cognitive behavioural therapy. These review authors concluded that cognitive behavioural therapy alone does not change post‐SCI pain intensity; however in combination with pharmacological treatment, it might be effective. We identified solely one randomised controlled trial with 61 participants. Results of this study are insufficient to permit firm conclusions about the effects of the behavioural program on pain.

A Cochrane review on non‐invasive brain stimulation for chronic pain covered several interventions (tDCS, rTMS and CES) that were within the scope of our review (O'Connell 2010). In addition to seven studies (Capel 2003; Defrin 2007; Kang 2009; Lefaucheur 2004; Lefaucheur 2006; Lefaucheur 2008; Tan 2006) with a focus on SCI, this review included pain trials conducted in patients with health conditions other than SCI. The review authors stated that low‐frequency rTMS was not effective in the treatment of chronic pain. For CES and tDCS, they found the evidence insufficient to allow conclusions on their effectiveness. Given that the scope of this review differed from the scope of ours, the findings are not fully comparable. Further, some of the included trials were evaluated differently: First, O'Connell 2010 included all three publications of Lefaucheur et al (Lefaucheur 2004; Lefaucheur 2006; Lefaucheur 2008) as separate trials, whereas we combined the data after clarification with the trialists. Second, the study of Defrin 2007 was included in their meta‐analysis, whereas we excluded it from our sensitivity analysis because of the substantial imbalance in pain scores seen at baseline and the resulting risk of bias.

We came across several studies on non‐pharmacological pain treatments that used study designs other than randomised trials (e.g. surveys). In a recent study, people with SCI were asked which non‐pharmacological pain treatments they perceived as most effective (Heutink 2011). Massage and relaxation therapy were mentioned most commonly. Acupuncture, physiotherapy and exercise, massage and relaxation and psychological treatments were found to be effective. In a survey in a Swedish SCI population, the participants rated TENS as minimally effective and physical training as more effective in reducing pain (Norrbrink 2004). Only half of the participants rated acupuncture as effective. In yet another survey of 120 people living with SCI pain, 47.5% of respondents reported a considerable pain reduction with physical therapy and 61.5% a slight reduction with psychological treatment (Widerstrom‐Noga 2003). Such cross‐sectional data might inform about the common use and perceived effects of non‐pharmacological pain treatments but cannot be compared directly with the results of trials designed to determine treatment effects.