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

By Jon-Kar Zubieta, Joshua A. Bueller, L. Jackson, David J. Scott, Yanjun Xu, Robert A. Koeppe, Thomas E. Nichols, C. Stohler. Journal of Neuroscience, 2005

803 citations recorded by the source corpus.

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 μ-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of μ-opioid receptor-mediated neurotransmission was observed in both higher-order and sub-cortical 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 μ-opioid receptor signaling in the human brain.

Subfields: Clinical Psychology, Cognitive Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/a9efe6826f52ec2925858b3efe792b42f3f8d860

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Citations in the corpus

Activation of the opioidergic descending pain control system underlies placebo analgesia. (2009, methodology): “The DLPFC (Zubieta et al., 2005) was corrected using a sphere of 15 mm radius.”
Neurobiological Mechanisms of the Placebo Effect (2005, background): “This was the case in the dorsolateral prefrontal cortex, pregenual anterior cingulate , anterior insular cortex, and nucleus accumbens (Zubieta et al., 2005b).”
The influence of negative emotions on pain: Behavioral effects and neural mechanisms (2009, positive): “Given that placebo analgesia is mediated by endogenous opioids at least in some conditions (Amanzio and Benedetti, 1999; Zubieta et al., 2005), the findings on the involvement of CCK in nocebo hyperalgesia suggest that the opioidergic and the CCKergic systems may be activated by opposite…”
Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. (2008, methodology): “In a previous study examining these processes using molecular imaging to monitor endogenous opioid activity on μ-opioid receptors, placebo-induced activation of this neurotransmitter system was observed in the rostral anterior cingulate, prefrontal and insular cortices, and nucleus accumbens.(18) Th”
A comprehensive review of the placebo effect: recent advances and current thought. (2008, methodology): “The direct demonstration of placeboinduced release of endogenous opioids has been obtained by using in vivo receptor binding with positron emission tomography by Zubieta et al. (2005).”
Traditional Chinese Acupuncture and Placebo (Sham) Acupuncture Are Differentiated by Their Effects on μ-Opioid Receptors (MORs) (2009, methodology): “Since placebo administration also induces activation of opioid receptors, specifically the μ-opioid receptor (MOR) class (Benedetti and Amanzio, 1997; Zubieta et al., 2005; Amanzio and Benedetti, 1999; Levine et al., 1978; Pomeranz and Chiu, 1976), acupuncture may indeed operate in part via placebo…”
The brain opioid theory of social attachment: a review of the evidence (2011, background): “…the fol licular and luteal phases of the female cycle appear to impact on the affinity of the MOR for opioid peptides which can lead to diurnal fluctuations in the functionality and impact of the endogenous opioids (Ikeda et al., 2005; Zubieta et al., 2005; Bodnar & Klein, 2006; Bodnar, 2007).”
Role of the Prefrontal Cortex in Pain Processing (2018, background): “Placebo-induced activation of μ-opioid receptor-mediated neurotransmission is found in both higher-order and subcortical brain regions, which include the pregenual and subgenual rostral ACC, DLPFC, insular cortex, and the nucleus accumbens [295].”
Functional grouping and cortical-subcortical interactions in emotion: A meta-analysis of neuroimaging studies (2008, positive): “Further, pgACC shows increases in activity and opioid release with placebo treatment in pain (Petrovic, Kalso, Petersson, & Ingvar, 2002; Wager, Rilling et al., 2004; Wager, Scott, & Zubieta, 2007; Zubieta et al., 2005).”
Reconsidering Anhedonia in Depression: Lessons from Translational Neuroscience (2010, background): “In humans, μ-opioid receptors in both the striatum and medial prefrontal cortex have been closely linked to affective responses (Liberzon et al., 2002; Zubieta et al., 2005; Zubieta et al., 2003; Zubieta et al., 2001).”