Neuromodulation of conditioned placebo/nocebo in heat pain: anodal vs cathodal transcranial direct current stimulation to the right dorsolateral prefrontal cortex

Abstract

Placebo and nocebo play an important role in clinical practice and medical research. Modulating placebo/nocebo responses using noninvasive brain stimulation methods, such as transcranial direct current stimulation (tDCS), has the potential to harness these effects to therapeutic benefit in a clinical setting. In this study, we assessed the effect of anodal and cathodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on conditioned placebo/nocebo cue response to heat pain. Two matched groups of healthy volunteers were subjected to an identical session of conditioning, during which low and high cues (abstract images) were associated with low and high pain levels, respectively. Twenty-minute 2-mA tDCS (either anodal or cathodal) over the rDLPFC was applied. The influence of tDCS current polarity (anodal vs cathodal) on placebo and nocebo was assessed, using subjects' pain ratings in response to identical pain preceded by the conditioned high or low cues. The duration of cue presentation varied to allow either fully conscious or subliminal processing. Significant placebo and nocebo effects in the anodal but not the cathodal group were elicited with the conditioning paradigm. This study provides evidence of a possibility to modulate the conditioned placebo and nocebo effect by changing the excitability of the rDLPFC using tDCS.

Figure 1. Experimental procedure

Conditioning phase, tDCS application, test phase, cue recognition test.

Figure 2. Main results

A. Subjective pain ratings by perception level (conscious/subliminal) by tDCS group (anodal vs. cathodal). Mean and standard error of mean (SEM) values are reported. B. Mixed linear regression analysis: mean values and slopes for pain ratings by tDCS group by perception level.