Neil E O'Connell

Rethinking Clinical Trials of Transcranial Direct Current Stimulation: Participant and Assessor Blinding Is Inadequate at Intensities of 2mA

Background Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding. Methods A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation. Results tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding. Conclusions Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution.

Chronic non-specific low back pain – sub-groups or a single mechanism?

BackgroundLow back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches.DiscussionMany clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient.An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention.SummaryThe disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed.

Is tactile acuity altered in people with chronic pain? A systematic review and meta-analysis

UNLABELLED Impaired tactile acuity in people with chronic pain conditions has been suggested to reflect altered cortical representation of the painful body part, and treatments that aim to improve tactile acuity in these conditions have shown clinical benefit. Whether abnormalities in tactile acuity are a consistent feature of chronic pain remains largely unknown. The aim of this review was to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is altered in people with chronic non-neuropathic pain. We systematically searched the literature for studies that investigated tactile acuity in people with chronic non-neuropathic pain and compared it to an appropriate control group. Sixteen studies, reporting data from 5 chronic pain conditions, were included. Data were available for 18 chronic pain populations (n = 484) and 15 control populations (n = 378). Our results suggest that tactile acuity is diminished in arthritis, complex regional pain syndrome, and chronic low back pain but not in burning mouth syndrome. The strength of the available evidence is weakened by somewhat inconsistent results and the high risk of bias observed in all of the included studies. PERSPECTIVE This systematic review synthesizes the evidence for tactile acuity deficits in people with chronic non-neuropathic pain. The findings suggest that tactile acuity deficits may be characteristic of chronic pain. That tactile acuity training may benefit those with chronic pain disorders suggests that clinical trials may be warranted.

Managing Chronic Nonspecific Low Back Pain With a Sensorimotor Retraining Approach: Exploratory Multiple-Baseline Study of 3 Participants

Background Current approaches to the management of chronic nonspecific low back pain (CNSLBP) have shown limited effectiveness. It appears that disruption of cortical structure and function is a feature of CNSLBP and that these changes may contribute to current treatment failures. Sensorimotor retraining approaches have been shown to be effective in the management of other long-standing pain problems that are characterized by cortical dysfunction. Similar treatments may be an option for people with CNSLBP. Objective The objectives of this study were to describe the effects of participation in a graded sensorimotor retraining program on pain intensity, interference of pain with daily life (pain interference), and self-reported disability and to evaluate the safety of the program. Design A multiple-baseline, replicated, single-case design was used for this study. Methods Three people with disabling CNSLBP were assessed weekly during a no-treatment baseline period. Each person then participated in a graded sensorimotor retraining program for a minimum of 10 weeks, during which clinical status was assessed weekly. Data collection continued weekly for 1 month after the end of formal treatment. Results Pain intensity, pain interference, and disability all were reduced, and the improvements were maintained throughout the follow-up period. No adverse reactions to treatment were reported. Limitations The findings are preliminary and were based on a single-case design. The observed improvements in clinical status may have been attributable to the effects of factors other than treatment, such as the effect of time and other, nonspecific effects. Conclusions Positive outcomes were reported for 3 participants with CNSLBP after the completion of a graded sensorimotor retraining program. However, the findings are only preliminary and require replication with more-robust study designs.

Seeing it helps: Movement-related back pain is reduced by visualization of the back during movement

Objectives: The aim of this study was to determine whether visualization of the back influenced parameters of movement-related pain in people with chronic nonspecific low back pain. Methods: We used a randomized cross-over experiment in which 25 participants performed repeated lumbar spine movements under 2 conditions. In the visual feedback condition, patients were able to visualize their back as it moved by the use of mirrors. In the control condition, the mirror was covered so no visualization of the back was possible. Results: The average postmovement pain intensity after participants had moved with visual feedback was less (35.5±22.8 mm) than when they moved without visual feedback (44.7±26.0 mm). This difference was statistically significant (mean difference=9.3, 95% confidence interval: 2.8-15.7 F(1,22)=8.82, P=0.007). The average time to ease after participants had moved with visual feedback was shorter (44.5 s±53.8) than when they moved without visual feedback (94.4 s±80.7). This difference was also statistically significantly (mean difference=49.9, 95% confidence interval: 19.3-80.6, F(1,22)=8.82, P=0.003). Discussion: Patients with chronic nonspecific low back pain reported less increase in pain and faster resolution of pain when moving in an environment that enabled them to visualize their back. This is consistent with emerging research on the use of mirror visual feedback in other long-standing pain problems and suggests that similar lines of inquiry may be worth pursuing in the chronic nonspecific low back pain population.

Transcranial direct current stimulation of the motor cortex in the treatment of chronic nonspecific low back pain: a randomized, double-blind exploratory study.

Objectives:To test the proof of principle that active anodal transcranial direct current stimulation (tDCS) applied to the motor cortex reduces pain significantly more than sham stimulation in a group of participants with chronic nonspecific low back pain. Methods:The study utilized a within-participants sham-controlled, interrupted time series design. A sample of 8 participants was recruited. After 3 days of baseline measures, patients entered a 15-day experimental period (Mondays to Fridays) for 3 consecutive weeks. During this period each patient received sham stimulation daily until a randomly allocated day when active stimulation was commenced. Active stimulation was then given daily for the remaining days of the experimental period. Both the participants and the assessors were blinded. The primary outcomes were average pain intensity and unpleasantness in the last 24 hours measured using a visual analogue scale. Secondary outcomes included self-reported disability, depression and anxiety, a battery of cognitive tests to monitor for unwanted effects of stimulation, and patients’ perceptions of whether they had received active or sham stimulation. Data were analyzed using generalized estimating equations. Results:No significant effect was seen in the primary outcomes between active and sham stimulation (average pain intensity P=0.821, unpleasantness P=0.937) or across any other clinical variables. There was evidence that patients may have been able to distinguish between the active and sham conditions (P=0.035). Discussion:These results do not provide evidence that tDCS is effective in the treatment of chronic back pain. The use of a small convenience sample limits the generalizability of these findings and precludes definitive conclusions on the efficacy of tDCS in chronic nonspecific low back pain.

Should we abandon cervical spine manipulation for mechanical neck pain? Yes.

Benedict Wand and colleagues argue that the risks of cervical spine manipulation are not justified, but David Cassidy and colleagues (doi:10.1136/bmj.e3680) think it is a valuable addition to patient care

Interpretive bias in acupuncture research? A case study

Acupuncture is one of the most widely used and broadly researched of the complementary and alternative therapies, but high-quality trials generally show no benefit over sham acupuncture. Many would view this result as evidence of ineffectiveness for this intervention. This discussion article focuses on the report of a large multicenter randomized controlled trial of acupuncture for chronic low-back pain (CLBP) in the lay and academic press, the ensuing discussion, and its impact on both clinical practice and service provision. The authors suggest that interpretive bias has affected reporting, leading to questionable conclusions and advocacy in favor of this form of care that may exceed the evidence. They also suggest that a lack of understanding of research into the placebo effect may have contributed to confusion in the interpretation of these trials.

How good is the neurophysiology of pain questionnaire? A Rasch analysis of psychometric properties.

UNLABELLED The Neurophysiology of Pain Questionnaire (NPQ) was devised to assess how an individual conceptualizes the biological mechanisms that underpin his or her pain. Despite its widespread use, its psychometric properties have not been comprehensively interrogated. Rasch analysis was undertaken on NPQ data from a convenience sample of 300 spinal pain patients, and test-retest reliability was assessed in a sample of 45 low back pain patients. The NPQ effectively targeted the ability of the sample and had acceptable internal consistency and test-retest reliability. However, some items functioned erratically for persons of differing abilities or were psychometrically redundant. The NPQ was reanalyzed with 7 questionable items excluded, and superior psychometric properties were observed. These findings suggest that the NPQ could be improved, but future prospective studies including qualitative measures are needed. In summary, the NPQ is a useful tool for assessing a patients conceptualization of the biological mechanisms that underpin his or her pain and for evaluating the effects of cognitive interventions in clinical practice and research. These findings suggest that it has adequate psychometric properties for use with chronic spinal pain patients. PERSPECTIVE Rasch analysis was used to analyze the NPQ. Despite several limitations, these results suggest that it is a useful tool with which to assess a patients conceptualization of the biological mechanisms that underpin his or her pain and to evaluate the effects of cognitive interventions in clinical practice and research.

Assessing self-perception in patients with chronic low back pain: Development of a back-specific body-perception questionnaire

BACKGROUND There is considerable interest in the role that disturbance of body-perception may play in long standing pain problems such as chronic low back pain (CLBP), both as a contributor to the clinical condition and as a potential target for treatment. In some chronic pain conditions body-perception has been investigated using self-report questionnaires. There is currently no questionnaire for assessing body-perception in people with CLBP. OBJECTIVE To describe the development of a back-specific body-perception questionnaire and examine the psychometrics of this new scale. METHODS Based on available evidence a back-specific body-perception questionnaire was developed. Fifty-one people with CLBP and an equal number of healthy controls completed the questionnaire; a subset of the patient population completed the questionnaire again one-week later. Scale-consistency and test-retest reliability were investigated on the patient sample. Validity was investigated by comparing responses between patients and controls as well as exploring the relationship between the questionnaire and important clinical characteristics. RESULTS All but one of the patients endorsed items on the questionnaire, which suggests that distorted body-perception may exist in this population. The internal-consistency and test-retest reliability of the scale appear acceptable. The discriminative validity of the questionnaire is supported by the marked differences in the questionnaire responses between patients and healthy controls and the construct validity by the significant association between the questionnaire score and important clinical variables. CONCLUSION Symptoms of body-perception distortion were endorsed by most CLBP patients, while these symptoms are very infrequent amongst healthy controls. Our results suggest the questionnaire has reasonable psychometric properties.