Document Detail

Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses.
MedLine Citation:
PMID:  18250260     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Placebo and nocebo effects, the therapeutic and adverse effects, respectively, of inert substances or sham procedures, represent serious confounds in the evaluation of therapeutic interventions. They are also an example of cognitive processes, particularly expectations, capable of influencing physiology. OBJECTIVE: To examine the contribution of 2 different neurotransmitters, the endogenous opioid and the dopaminergic (DA) systems, to the development of placebo and nocebo effects. DESIGN AND SETTING: Using a within-subject design, subjects twice underwent a 20-minute standardized pain challenge, in the absence and presence of a placebo with expected analgesic properties. Studies were conducted in a university hospital setting. PARTICIPANTS: Twenty healthy men and women aged 20 to 30 years recruited by advertisement. MAIN OUTCOME MEASURES: Activation of DA and opioid neurotransmission by a pain stressor with and without placebo (changes in the binding potential of carbon 11 [11C]-labeled raclopride and [11C] carfentanil with positron emission tomography) and ratings of pain, affective state, and anticipation and perception of analgesia. RESULTS: Placebo-induced activation of opioid neurotransmission was detected in the anterior cingulate, orbitofrontal and insular cortices, nucleus accumbens, amygdala, and periaqueductal gray matter. Dopaminergic activation was observed in the ventral basal ganglia, including the nucleus accumbens. Regional DA and opioid activity were associated with the anticipated and subjectively perceived effectiveness of the placebo and reductions in continuous pain ratings. High placebo responses were associated with greater DA and opioid activity in the nucleus accumbens. Nocebo responses were associated with a deactivation of DA and opioid release. Nucleus accumbens DA release accounted for 25% of the variance in placebo analgesic effects. CONCLUSIONS: Placebo and nocebo effects are associated with opposite responses of DA and endogenous opioid neurotransmission in a distributed network of regions. The brain areas involved in these phenomena form part of the circuit typically implicated in reward responses and motivated behavior.
David J Scott; Christian S Stohler; Christine M Egnatuk; Heng Wang; Robert A Koeppe; Jon-Kar Zubieta
Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Archives of general psychiatry     Volume:  65     ISSN:  1538-3636     ISO Abbreviation:  Arch. Gen. Psychiatry     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-05     Completed Date:  2008-02-21     Revised Date:  2008-10-31    
Medline Journal Info:
Nlm Unique ID:  0372435     Medline TA:  Arch Gen Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  220-31     Citation Subset:  AIM; IM    
Department of Psychiatry and Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor 48109-0720, USA.
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MeSH Terms
Analgesics / therapeutic use*
Brain / physiopathology*,  radionuclide imaging
Brain Mapping
Carbon Radioisotopes
Fentanyl / analogs & derivatives,  diagnostic use
Image Processing, Computer-Assisted
Pain / drug therapy*,  physiopathology*
Pain Measurement
Placebo Effect*
Positron-Emission Tomography
Raclopride / diagnostic use
Receptors, Dopamine / physiology*
Receptors, Dopamine D2 / physiology
Receptors, Dopamine D3 / physiology
Receptors, Opioid / physiology*
Receptors, Opioid, mu / physiology
Synaptic Transmission / physiology
Grant Support
Reg. No./Substance:
0/Analgesics; 0/Carbon Radioisotopes; 0/Receptors, Dopamine; 0/Receptors, Dopamine D2; 0/Receptors, Dopamine D3; 0/Receptors, Opioid; 0/Receptors, Opioid, mu; 437-38-7/Fentanyl; 59708-52-0/carfentanil; 84225-95-6/Raclopride
Comment In:
Arch Gen Psychiatry. 2008 Oct;65(10):1225-6; author reply 1226   [PMID:  18838641 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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