Independent effects of transcranial direct current stimulation and social influence on pain

Abstract

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulatory technique with the potential to provide pain relief. However, tDCS effects on pain are variable across existing studies, possibly related to differences in stimulation protocols and expectancy effects. We investigated the independent and joint effects of contralateral motor cortex tDCS (anodal vs cathodal) and socially induced expectations (analgesia vs hyperalgesia) about tDCS on thermal pain. We employed a double-blind, randomized 2 × 2 factorial cross-over design, with 5 sessions per participant on separate days. After calibration in Session 1, Sessions 2 to 5 crossed anodal or cathodal tDCS (20 minutes 2 mA) with socially induced analgesic or hyperalgesic expectations, with 6 to 7 days between the sessions. The social manipulation involved videos of previous "participants" (confederates) describing tDCS as inducing a low-pain state ("analgesic expectancy") or hypersensitivity to sensation ("hyperalgesic expectancy"). Anodal tDCS reduced pain compared with cathodal stimulation (F(1,19.9) = 19.53, P < 0.001, Cohen d = 0.86) and analgesic expectancy reduced pain compared with hyperalgesic expectancy (F(1,19.8) = 5.62, P = 0.027, Cohen d = 0.56). There was no significant interaction between tDCS and social expectations. Effects of social suggestions were related to expectations, whereas tDCS effects were unrelated to expectancies. The observed additive effects provide novel evidence that tDCS and socially induced expectations operate through independent processes. They extend clinical tDCS studies by showing tDCS effects on controlled nociceptive pain independent of expectancy effects. In addition, they show that social suggestions about neurostimulation effects can elicit potent placebo effects.

Figure 1.

Overview of paradigm and design.

Figure 2.

Calibration procedure and results.

Figure 3.

Expectations and tDCS sensations. (a)-(b): 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). (c)-(d): no significant difference between the sensations evoked by each type of tDCS (p > 0.05).

Figure 4.

Main findings. (a): Treatment effects (Post-treatment - Pre-treatment change or “delta” values) for each of the four experimental conditions, and for each of high-temperature (left panel) and low-temperature (right panel) heat. Error bars reflect standard errors of the mean (s.e.m.) after adjusting for random effects of participant [75] (b): The effects of stimulation (anodal vs. cathodal), Social Manipulation (analgesia vs. hyperalgesia) and Temperature (high vs. low). Dots reflect the effect magnitude estimates for individual participants. Error bars reflect the s.e.m.

Figure 5.

Mediation results. Path a1: Social -> Expectancy (Social Manipulation effects on expectancy). b: Expectancy -> Pain (expectancy effects on pain controlling for Social Manipulation). c1’: Social -> Pain (the direct effect of Social Manipulation on pain controlling for the mediator (expectation)). c1: Social -> Pain (the total effect of Social Manipulation on pain). a1b: Mediation of social effects on pain by expectancy. a2: tDCS stimulation -> Expectancy (tDCS stimulation (anodal and cathodal) effects on expectancy). b: Expectancy -> Pain (expectancy effects on pain controlling for stimulation type (anodal and cathodal)). c2’: tDCS stimulation (anodal and cathodal)-> Pain (the direct effect of Social Manipulation on pain controlling for the mediator (expectation)). c2: tDCS stimulation (anodal and cathodal) -> Pain (the total effect of stimulation type on pain). a2b: Mediation of stimulation type effects on pain by expectancy.