What does tDCS do for pain?

We’ve heard a lot about non-invasive electrical brain stimulation recently (e.g. Body in Mind blog post tDCS – negotiating the ‘rising tide’ of hype), but does it really work for chronic pain? Well, some people who conducted trials in chronic pain populations claim it does [e.g. 1–5], but taking a closer look at the evidence is disappointing: the level of evidence is low and consists of studies with small sample sizes and a high risk of bias due to a range of methodological flaws (such as participant and therapist blinding – see Neil O’Connell’s post: ‘A big hole in the control? Transcranial direct current stimulation blinding on trial‘ and the published paper [13]). Recent systematic reviews and meta-analyses concluded that there is a low level of evidence that tDCS has either a small pain reducing effect [11] or is not effective [14].

So what is really going on? We recently conducted a trial to watch the brain (in an fMRI scanner) while it processes heat pain [7]. This was done before and after we applied anodal, cathodal or sham tDCS (in randomised order). The idea was to evaluate whether anodal or cathodal tDCS changes pain processing compared to sham stimulation and whether specific brain areas were particularly affected by the tDCS intervention.

The results were not very convincing: neither anodal nor cathodal stimulation had any significant effect on brain processing when compared to sham stimulation. Only when we directly tested anodal versus cathodal stimulation (a so-called interaction analysis which takes advantage of the fact that the supposed effects would, in fact, be in opposite directions) could we see statistically significant results. The careful interpretation of this result is that if there is an influence of tDCS on pain processing in the brain, it is rather small. In concordance with these very small effects, the pain intensity perceived by our participants did not change much after anodal or cathodal stimulation. However, this very small effect occurred in the predicted direction: anodal stimulation compared to cathodal stimulation resulted in a decreased regional cerebral blood flow, indicating reduced cortical pain processing (hence there is an effect, but it is subclinical, as this change in brain activity did not change the perception of nociceptive input).

There is a range of possible explanations for our results. The easiest would be: tDCS does not work, and pain processing and pain perception cannot be altered by applying electricity to the outside of the skull. But somehow this seems too simplistic, and makes it difficult to explain why other techniques (such as pain-evoked potentials) have identified alterations in brain excitability fairly consistently [2,8–10,12]. The more likely explanation lies within the often-cited multidimensional nature of pain. Citing from our paper,

Pain perception depends on a range of different pathways as the evaluation of pain is a more complex process than mere somatosensory processing in evoked potentials.

We will leave you to ponder this almost philosophical statement and we look forward to hear your thoughts.

Best wishes

Kerstin Luedtke

photo_Kerstin

Kerstin Luedtke completed her training as a physiotherapist in 1993 and is currently a postdoctoral researcher at the Institute of Systems Neurosciences, University Hospital Hamburg-Eppendorf, Germany. She completed her PhD at the University of Birmingham, UK investigating transcranial direct current stimulation over the motor cortex for the reduction of chronic low back pain.

Arne May

Arne MayArne May is a Professor of Neurology in the Department of Systems Neuroscience at the University of Hamburg and head of the headache outpatient clinic of the University clinic of Hamburg. His major research interests are the basic mechanisms of headpain, the chronification of pain and plasticity within the human brain. The work of his group involves human imaging studies in primary headache as well as experimental studies of trigeminovascular nociception, with the aim of understanding how to modulate headache syndromes and chronicity of pain. Prior to his position at the University of Hamburg, Professor May was a clinician and conducted research into pain and headache syndromes at the University of Regensburg. Prior to this he completed his residency in the Neurology Department of the University of Essen, followed by post-doctorate studies at the Institute of Neurology in London. Professor May is currently the vice-president of the German Headache Society and a member of the Board of trustees of the International Headache Society since 2013. He has published over 180 original and review articles and is an Associate Editor of Cephalalgia, Journal of Headache & Pain and Der Schmerz.

References

[1]     Boggio PS, Amancio EJ, Correa CF, Cecilio S, Valasek C, Bajwa Z, Freedman SD, Pascual-Leone A, Edwards DJ, Fregni F. Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study. Clin J Pain 2009;25:691–5.

[2]     Csifcsak G, Antal A, Hillers F, Levold M, Bachmann CG, Happe S, Nitsche MA, Ellrich J, Paulus W. Modulatory effects of transcranial direct current stimulation on laser-evoked potentials. Pain Med 2009;10:122–32.

[3]     Dasilva AF, Mendonca ME, Zaghi S, Lopes M, Dossantos MF, Spierings EL, Bajwa Z, Datta A, Bikson M, Fregni F. tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine. Headache 2012;52:1283–95.

[4]     Fenton BW, Palmieri PA, Boggio P, Fanning J, Fregni F. A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain. Brain Stimul 2009;2:103–7.

[5]     Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain 2006;122:197–209.

[6]     Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum 2006;54:3988–98.

[7]     Ihle K, Rodriguez-Raecke R, Luedtke K, & May A (2014). tDCS modulates cortical nociceptive processing but has little to no impact on pain perception. Pain, 155 (10), 2080-7 PMID: 25083928

[8]     Kumru H, Soler D, Vidal J, Navarro X, Tormos JM, Pascual-Leone A, Valls-Sole J. The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: An evoked potentials and quantitative thermal testing study. Eur J Pain. doi:10.1002/j.1532-2149.2012.00167.x.

[9]     Kwon YH, Ko MH, Ahn SH, Kim YH, Song JC, Lee CH, Chang MC, Jang SH. Primary motor cortex activation by transcranial direct current stimulation in the human brain. Neurosci Lett 2008;435:56–9.

[10]   Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res 2004;156:439–43.

[11]   Luedtke K, Rushton A, Wright C, Geiss B, Juergens TP, May A. Transcranial direct current stimulation for the reduction of clinical and experimentally induced pain: a systematic review and meta-analysis. Clin. J. Pain 2012;28:452–461.

[12]   Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation–technical, safety and functional aspects. Suppl Clin Neurophysiol 2003;56:255–76.

[13]   O’Connell NE, Cossar J, Marston L, Wand BM, Bunce D, Moseley GL, De Souza LH. Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA. PloS One 2012;7:e47514.

[14]   O’Connell NE, Wand BM, Marston L, Spencer S, Desouza LH. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst. Rev. 2014;4:CD008208.