Both placebo and nocebo studies are important research issues with broad implications for human self-healing and self-harming. Placebo analgesia and nocebo hyperalgesia are the most robust placebo and nocebo effects, and these effects provide a unique example of how contextual learning/conditioning can either relieve or aggravate our pain experience. Previous studies have demonstrated that both placebo analgesia and nocebo hyperalgesia derive from highly active neural process involving multiple brain regions and neurotransmitters. Studies also indicate that no single neurobiological mechanism can explain both effects. Thus, the crucial next step is to perform comparative studies of different placebo analgesia effects and ascertain how they differ from nocebo hyperalgesia in order to distinguish the different neural mechanisms underlying these important clinical phenomena. Using an innovative brain imaging technique, this proposed study attempts to address two questions: 1) what are the distinct brain mechanisms of placebo effects due to opioid and non-opioid conditioning? and 2) Does a common brain network mediate expectancy-evoked placebo analgesia and nocebo hyperalgesia? Our mechanistic investigation will compare different pharmacological conditioning paradigms (including opioid and non-opioid conditioning) using an integrated MR-PET system, and different experiential expectancy manipulation paradigms (placebo analgesia and nocebo hyperalgesia) using fMRI. Answering these questions will significantly advance our understanding of placebo/nocebo effects, facilitate the development of new methods to harness (or avoid) these self- healing (or self-harming) capacities, inform us on how previous experiences can consciously (by expectation) and unconsciously (by conditioning) sculpt our brain response, and shed light on our understanding of basic principles of brain function, pain perception, and pain modulation.

Public Health Relevance

Both placebo and nocebo responses have significant clinical implications. The aim of this study is to investigate the brain mechanisms of placebo and nocebo effects to facilitate methods to harness or avoid these self-healing and self-harming capacities, respectively.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AT006364-04
Application #
8654304
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Huntley, Kristen V
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Rong, Peijing; Liu, Jun; Wang, Liping et al. (2016) Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. J Affect Disord 195:172-9
Fang, Jiliang; Rong, Peijing; Hong, Yang et al. (2016) Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry 79:266-73
Wang, Xiaoyun; Wang, Zengjian; Liu, Jian et al. (2016) Repeated acupuncture treatments modulate amygdala resting state functional connectivity of depressive patients. Neuroimage Clin 12:746-752
Tao, Jing; Liu, Jiao; Egorova, Natalia et al. (2016) Increased Hippocampus-Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults. Front Aging Neurosci 8:25
Li, Zhengjie; Liu, Mailan; Lan, Lei et al. (2016) Altered periaqueductal gray resting state functional connectivity in migraine and the modulation effect of treatment. Sci Rep 6:20298
Hwang, J W; Xin, S C; Ou, Y M et al. (2016) Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals. J Psychiatr Res 76:111-20
Egorova, Natalia; Park, Joel; Orr, Scott P et al. (2015) Not seeing or feeling is still believing: conscious and non-conscious pain modulation after direct and observational learning. Sci Rep 5:16809
Ahmari, Susanne E; Dougherty, Darin D (2015) DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS. Depress Anxiety 32:550-62
Egorova, Natalia; Yu, Rongjun; Kaur, Navneet et al. (2015) Neuromodulation of conditioned placebo/nocebo in heat pain: anodal vs cathodal transcranial direct current stimulation to the right dorsolateral prefrontal cortex. Pain 156:1342-7
Freeman, Sonya; Yu, Rongjun; Egorova, Natalia et al. (2015) Distinct neural representations of placebo and nocebo effects. Neuroimage 112:197-207

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