Manipulating placebo analgesia and nocebo hyperalgesia by changing brain excitability

Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain’s de...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2021-05, Vol.118 (19), p.1-11
Main Authors: Tu, Yiheng, Wilson, Georgia, Camprodon, Joan, Dougherty, Darin D., Vangel, Mark, Benedetti, Fabrizio, Kaptchuk, Ted J., Gollub, Randy L., Kong, Jian
Format: Article
Language:English
Subjects:
Analgesia
Biological Sciences
Brain
Clinical trials
Direct current
Electrical stimulation of the brain
ESB
Excitability
Expectancy
Functional magnetic resonance imaging
Hyperalgesia
Medical practices
Medical research
Neural networks
Nocebos
Pain
Pain perception
Placebo effect
Placebos
Prefrontal cortex
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Summary:Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain’s descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2101273118