Neuromodulation of conditioned placebo/nocebo in heat pain

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 the present study we assessed the effect of anodal and cathodal tDCS over the right DLPFC 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 2mA tDCS (either anodal or cathodal) over the right DLPFC 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 right DLPFC using tDCS.

Transcranial Direct Current Stimulation (tDCS) Targeting Left Dorsolateral Prefrontal Cortex Modulates Task-Induced Acute Pain in Healthy Volunteers

“…Recently, investigators have begun exploring the role of DLPFC in placebo analgesia (61). Current tDCS efforts targeting DLPFC attempt to modulate placebo analgesia (62) and fear vigilance (63), with the hope that these approaches may yield novel pain treatments. For these and other approaches, rigorous double-blinded, sham-controlled studies will be needed in chronic pain populations, using tDCS designed to engage a variety of cortical targets associated with the affective, cognitive, and attentional aspects of pain.…”

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study

“…A 1 × 3 grid was drawn on the medial surface of the affected knee, avoiding the patella. Then, calibrated thermal heat pain stimuli were delivered to the medial side of the affected knee using a PATHWAY system with a 3 cm × 3 cm probe ( Egorova et al, 2015b ; Egorova et al, 2015c ). Each stimulus was initiated at a 32 °C baseline and increased to a target temperature that was presented for 12 s, including 2.5 s to ramp up and ramp down.…”

The placebo effect: From concepts to genes

“…Consistent with this, placebo effects appear weaker in patients with Alzheimer Disease, with the loss of prefrontal executive function negatively correlating with the strength of placebo effect (Benedetti et al, 2006). These studies provide strong evidence that the DLPFC is crucial in the processing of placebo and nocebo effects and that it is feasible to modulate conditioned placebo and nocebo effect by changing the excitability of the rDLPFC using tDCS (Egorova et al, 2015). This is perhaps not surprising given that the DLPFC has been associated with a wide range of cognitive processes, including emotion regulation (Ochsner and Gross, 2005), working memory (Petrides, 2000), and cognitive control (Miller and Cohen, 2001).…”