Non-invasive brain stimulation techniques for chronic pain. A report of a Cochrane systematic review and meta-analysis

Background: Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS). Aim: To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. Design: A Cochrane systematic review with meta-analyses. Methods: We employed a comprehensive search strategy. Randomised and quasi-randomised studies of rTMS, CES or tDCS were included if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. Where possible we entered data into meta-analyses. Results: We included 33 trials in the review (19 rTMS, eight CES and six tDCS). Only one study was judged as being at low risk of bias. Studies of rTMS demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective. A short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies was suggested (standardised mean difference (SMD) -0.40, 95% confidence interval (CI) -0.26 to -0.54, P \u3c 0.00001). This equates to a 15% (95% CI 10% to 20%) reduction in pain which does not clearly exceed the pre-established criteria for a minimally clinically important difference (\u3e 15%). For CES (four studies, 133 participants) no statistically significant difference was found between active stimulation and sham. Analysis of tDCS studies (five studies, 83 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation. Pre-specified subgroup analysis of tDCS applied to the motor cortex suggested superiority of active stimulation over sham (SMD -0.59, 95% CI -1.10 to -0.08). Non-invasive brain stimulation appears to be associated with minor and transient side effects. Conclusion: Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. The effects do not clearly exceed the predetermined threshold of minimal clinical significance. Low-frequency rTMS is not effective in the treatment of chronic pain. There is insufficient evidence from which to draw firm conclusions regarding the efficacy of CES or tDCS. The available evidence suggests that tDCS applied to the motor cortex may have short-term effects on chronic pain and that CES may be ineffective. There is a need for further, rigorously designed studies of all types of stimulation