Background & Aims
Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique widely used for its potential effects on brain network dynamics and behaviors [1,2]. It has also been found to be an effective treatment for a variety of pain conditions [3]. Nevertheless, previous tDCS studies investigating its impact on pain-relief have high variability in their results, which may originate from either the usage of different stimulation types or ignoring relevant psychological factors [4,5]. In the field of brain stimulation, psychological factors including expectation and social manipulation are rarely investigated, despite the fact that they have been shown to independently impact treatment outcomes [6-8]. In this double-blind, randomized cross-over study, we aimed to investigate the effects of anodal/cathodal tDCS of the left motor cortex (M1) and positive/negative social manipulations on pain responses in 20 healthy participants.
Methods
Our study consisted of five different sessions. Participants first completed an initial pain calibration session to find two temperatures and two skin sites on the right forearm for heat stimulation. The remaining four sessions consisted of anodal/cathodal tDCS stimulation and positive/negative social modeling, paired with pain trials both before and after tDCS, with 6-7 day intervals between each session. The social modeling manipulation consisted of simple text and video presentation of a mock previous participant’s positive or negative experience with tDCS. The tDCS device was applied at 2 mA for 20 minutes with electrodes placed on the C3 (anode) and FP2 (cathode) regions according to the 10-10 EEG system. We constructed mixed-effect models for all trials including both random intercepts and slopes for tDCS Type, Social Modeling condition, and stimulus intensity.
Results
The expectation of experiencing lower pain after analgesic expectancy induced videos was significantly higher than after hyperalgesic expectancy induced videos (p < 0.05), and the expectation of experiencing higher pain after hyperalgesic expectancy induced videos was significantly higher than after analgesic expectancy induced videos (p < 0.05). Pain was significantly reduced for anodal relative to cathodal stimulation (main effect of tDCS Type (F(1,19.9) = 19.53, p < 0.001, Cohen’s d?=?0.86). Pain was also significantly reduced for analgesic vs. hyperalgesic expectancy (main effect of Social Modeling, F(1,19.8) = 5.62, p = 0.027, Cohen’s d?=?0.56, and there was no significant tDCS Type x Social Modeling interaction (p = 0.267).
Conclusions
In this study, we examined the impact of tDCS, social manipulation, and their interactions on pain relief. Unlike previous tDCS studies in pain relief, this novel research considered the role of expectation in response to tDCS, which were manipulated towards either the effectiveness or ineffectiveness of this treatment. Results from our statistical models showed that anodal M1 stimulation resulted in lower reported pain compared to cathodal stimulation, and analgesic expectancy social manipulation was more effective than hyperalgesic expectancy social manipulation. Future studies may use functional magnetic resonance imaging to deepen our understanding of the functional mechanisms of tDCS on pain relief.
References
1. Moffa AH, Brunoni AR, Nikolin S, Loo CK. Transcranial Direct Current Stimulation in Psychiatric Disorders: A Comprehensive Review. Psychiatr Clin North Am. 2018;41(3):447-463.
2. Filmer HL, Mattingley JB, Dux PE. Modulating brain activity and behaviour with tDCS: Rumours of its death have been greatly exaggerated. Cortex. 2020;123:141-151.
3. Yang S, Chang MC. Transcranial Direct Current Stimulation for the Management of Neuropathic Pain: A Narrative Review. Pain Physician. 2021;24(6):E771-E781.
4. Rabipour S, Wu AD, Davidson PSR, Iacoboni M. Expectations May Influence the Effects of Transcranial Direct Current Stimulation. 2018. doi:10.1101/279554
5. Braga M, Barbiani D, Emadi Andani M, Villa-Sánchez B, Tinazzi M, Fiorio M. The Role of Expectation and Beliefs on the Effects of Non-Invasive Brain Stimulation. Brain Sci. 2021;11(11). doi:10.3390/brainsci11111526
6. Ashar YK, Chang LJ, Wager TD. Brain Mechanisms of the Placebo Effect: An Affective Appraisal Account. Annu Rev Clin Psychol. 2017;13:73-98.
7. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet. 2010;375(9715):686-695.
8. Colloca L. The Placebo Effect in Pain Therapies. Annu Rev Pharmacol Toxicol. 2019;59:191-211.