The Cochrane Pain, Palliative and Supportive Care Group has been producing Cochrane Reviews for more than 20 years, including dozens covering a wide range of therapies for pain. In April 2018, their review of brain stimulation for chronic pain was updated and lead author Neil E O'Connell from Brunel University London in the UK tells us about the latest evidence in this podcast.
John: Hello, I'm John Hilton, editor in the Cochrane Editorial and Methods department. The Cochrane Pain, Palliative and Supportive Care Group has been producing Cochrane Reviews for more than 20 years, including dozens covering a wide range of therapies for pain. In April 2018, their review of brain stimulation for chronic pain was updated and lead author Neil E O'Connell from Brunel University London in the UK tells us about the latest evidence in this podcast.
Neil: Ten to twenty people in every hundred experience significant chronic pain, and many of these receive inadequate pain management. Brain stimulation techniques use electrical currents to try to reduce pain by altering the activity in the areas of the brain that are involved in pain processing. The techniques vary and can be invasive, where electrodes are implanted in brain tissue, and non-invasive, where no surgical procedure is required. We looked into the effects of the latter, reviewing non-invasive brain stimulation techniques compared with sham, or placebo, stimulation; and found little or no evidence of benefit.
Our review examines three broad classes of treatment. The main one being repetitive transcranial magnetic stimulation (rTMS). This involves stimulation of the outer layer of the brain with a coil applied to the scalp. It uses rapidly changing magnetic fields to induce electric currents in brain tissue, causing alterations in brain activity. The other two classes are transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES), which involve application of low intensity electrical current to the brain.
This update of our 2014 review adds a further 38 trials, with more than 1200 additional participants, so that we now have a total of nearly 3000 patients in 94 trials.
When we pooled the results of the studies of rTMS, we found low quality evidence of a very small effect on pain intensity in the short term but with lots of variability across the results. For example, there was very low quality evidence of a short-term effect on pain intensity of high-frequency rTMS of the motor cortex in single-dose studies, which equates to a small reduction in pain that is unlikely to be clinically meaningful. The results of the multiple dose studies were particularly scattered and did not demonstrate a significant effect.
The evidence from tDCS studies was also of very low quality and it showed a small effect of tDCS compared with sham, which would amount to an average improvement of around one sixth in pain intensity, equivalent to dropping less than one point on a 10-point pain scale.
Finally, data from 270 participants in six studies of CES also provides low quality evidence, with no clear difference between patients in the active and sham stimulation groups.
Alongside this lack of clear benefit, the reporting of adverse events was inconsistent across the studies and was often missing or incomplete. So it’s not possible to conclude confidently that the techniques are safe.
Coupled with all of this, the risks of bias in the studies and their generally small size make our estimates imprecise and even the small effect we found is likely exaggerated. Therefore, although our analyses appear to show some small reductions in pain with tDCS and rTMS, there is not convincing evidence of an important benefit.
One of the key take home messages therefore is that despite such a large number of published trials, the continuing substantial uncertainty as to the benefits of non-invasive brain stimulation for chronic pain speaks to a problem of research waste in this field of study. We need to see fewer but larger, better designed and well reported trials if this uncertainty is to be reduced.
John: If you would like to look in more detail at the nearly 100 trials that Neil and his fellow reviewers identified and watch for further updates of the review should those definitive trials be done, the full review is free to view in the Cochrane Library. Just go online to Cochrane Library dot com and search 'brain stimulation for chronic pain'.