Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors

Abstract

Reductions in pain ratings when administered a placebo with expected analgesic properties have been described and hypothesized to be mediated by the pain-suppressive endogenous opioid system. Using molecular imaging techniques, we directly examined the activity of the endogenous opioid system on -opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of -opioid receptor-mediated neurotransmission was observed in both higher-order and subcortical brain regions, which included the pregenual and subgenual rostral anterior cingulate, the dorsolateral prefrontal cortex, the insular cortex, and the nucleus accumbens. Regional activations were paralleled by lower ratings of pain intensity, reductions in its sensory and affective qualities, and in the negative emotional state of the volunteers. These data demonstrate that cognitive factors (e.g., expectation of pain relief) are capable of modulating physical and emotional states through the site-specific activation of -opioid receptor signaling in the human brain.

Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

“…Additional regions where endogenous opioid responses to placebo administration were predicted by these personality traits largely overlap with those identified in previous reports as responsive to placebo administration and involved in the regulation of the pain experience Wager et al, 2007;Zubieta et al, 2005): subgenual ACC, dorsal ACC, OFC, anterior and posterior insula, amygdala and, at lower thresholds, PAG, thalamus and dorsolateral prefrontal cortex. As previously observed, activation of m-opioid receptor mediated neurotransmission in some of these regions were associated with reductions in individual pain report.…”

New concept for backache: biopsychosocial pain syndrome

“…Recent development in brain science indicates that placebo stimulates brain and activates pain relief processes and that anticipation of pain relief stimulates brain activity [74]. Placebo induces activation of chemical substance in the brain (endogenous opioid) [77]. Another study reports that mortality is decreased by placebo in patients who comply with treatment [76].…”

Placebo mechanisms across different conditions: from the clinical setting to physical performance

“…While these results were stimulating, they did not yet establish a causality link. Shortly afterwards, Zubieta et al [22] provided in another PET study a direct demonstration of endogenous opioid release in the course of an experimental pain protocol with placebo manipulation in healthy volunteers. They employed a molecular imaging technique, whereby [ 11 C]carfentanil, a m-opioid receptor-selective radiotracer, binds to in vivo available m-opioid receptors.…”