Placebo and Nocebo Effects Are Defined by Opposite Opioid and Dopaminergic Responses

Scott, David J.; Stohler, Christian S.; Egnatuk, Christine M.; Wang, Heng; Koeppe, Robert A.; Zubieta, Jon Kar

doi:10.1001/archgenpsychiatry.2007.34

Cited by 553 publications

(516 citation statements)

References 73 publications

(121 reference statements)

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“…The key role of interconnected endogenous opioid and DAergic systems in mood control is demonstrated by the facilitation of antidepressant-like effects of RB101 after deafferentation of the DAergic mesolimbic pathway (Cordonnier et al, 2005), which increases the concentrations of PENK and ENKs. Taken together, these results suggest a phasic control of the DAergic mesolimbic pathway by ENKs, which may be impaired in depressive-like syndromes, and clinical studies are starting to investigate this endogenous opioid-DA interaction in human depression (Kennedy et al, 2006;Scott et al, 2008). The development of (i) dual orally active ENK inhibitors with strong analgesic properties and immediate antidepressant effects (Noble and Roques, 2007) and (ii) delta agonists devoid of side effects may lead to significant improvements in the treatment of depression and mood disorders.…”

mentioning

confidence: 99%

Endogenous Opioids as Physiological Antidepressants: Complementary Role of Delta Receptors and Dopamine

Jutkiewicz

Roques

2011

Neuropsychopharmacol

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mentioning

confidence: 99%

Endogenous Opioids as Physiological Antidepressants: Complementary Role of Delta Receptors and Dopamine

Jutkiewicz

Roques

2011

Neuropsychopharmacol

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“…Activity in these regions predicts individual placebo analgesia more accurately than regions involved in cognitive control or pain processing (21). This network is dependent on endogenous opioids (16,19,22) and interacts with the mesolimbic dopamine system (23)(24)(25) to reduce pain by inhibiting nociceptive signaling (15). Because these regions collectively are involved in valuation and reward-related processing more generally (26,27), and for reasons of clarity and brevity, we will refer to this set of regions as "emotion appraisal circuitry.…”

mentioning

confidence: 99%

Placebo improves pleasure and pain through opposite modulation of sensory processing

Ellingsen

Wessberg

Eikemo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Placebo analgesia is often conceptualized as a reward mechanism. However, by targeting only negative experiences, such as pain, placebo research may tell only half the story. We compared placebo improvement of painful touch (analgesia) with placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a crossover design. Somatosensory processing was decreased during placebo analgesia and increased during placebo hyperhedonia. Both placebo responses were associated with similar patterns of activation increase in circuitry involved in emotion appraisal, including the pregenual anterior cingulate, medial orbitofrontal cortex, amygdala, accumbens, and midbrain structures. Importantly, placebo-induced coupling between the ventromedial prefrontal cortex and periaqueductal gray correlated with somatosensory decreases to painful touch and somatosensory increases to pleasant touch. These findings suggest that placebo analgesia and hyperhedonia are mediated by activation of shared emotion appraisal neurocircuitry, which down-or upregulates early sensory processing, depending on whether the expectation is reduced pain or increased pleasure.expectancy | neuroimaging | hedonic feelings M edical treatments aim to provide relief from pain and aversive states. Consequently, research on placebo effects has focused on relief of negative hedonic feelings, like pain and displeasure (1). In contrast, placebo improvement of positive hedonics has received little attention. However, pain and pleasure processes are tightly linked. Relief from pain can induce a pleasant experience underpinned by activation of reward neurocircuitry (2-4). Moreover, a painful stimulus can even be perceived as pleasant when it represents relief from a more severe outcome (5). In line with this pain-pleasure link, placebo analgesia can be conceptualized as a type of reward mechanism; pain relief is a better outcome than the alternative (6-8) and is typically framed as a gain (improvement of pain) (9).Like pain, pleasure is greatly affected by context and expectation (10). Manipulation of people's beliefs about the price of a wine (11), the amount of fruit in a sweet drink (12), the richness of a skin cream (13), and who is caressing them (14) alters the experienced pleasantness of these stimuli.Placebo-induced improvement of aversive experiences (e.g., pain, anxiety, unpleasant taste) is often underpinned by a decrease in central sensory processing. Placebo analgesia is characterized by decreases in the thalamus, posterior insula (pINS), and primary and secondary somatosensory areas (SI and SII) (15)(16)(17). Placebo reduction of affective responses to unpleasant visual stimuli is similarly underpinned by suppression of visual processing (8). It is not, however, known whether placeboenhanced pleasantness (i.e., hyperhedonia) also alters early stages of sensory processing, or if this change is encoded in higher-level valuation areas.Functional neuroimaging studies have revealed that the ventromedial prefrontal cortex (vmPFC), amygdala, ventral...

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“…In healthy volunteers, diazepam was able to block the nocebo response (Scott, Stohler, Egnatuk, Wang, Koeppe & Zubieta, 2008). These curious responses are not entirely dependent on conscious perception of cues since they may be generated by unconscious cues as well (Jensen et al, 2012).…”

Section: Neurobiology Of Negative Expectationsmentioning

confidence: 94%

Nocebo phenomenon

Peci¹,

Peci²

2016

Neuropsychological Trends

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Placebo and Nocebo Effects Are Defined by Opposite Opioid and Dopaminergic Responses

Abstract: 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.

Cited by 553 publications

References 73 publications

Endogenous Opioids as Physiological Antidepressants: Complementary Role of Delta Receptors and Dopamine

Endogenous Opioids as Physiological Antidepressants: Complementary Role of Delta Receptors and Dopamine

Placebo improves pleasure and pain through opposite modulation of sensory processing

Nocebo phenomenon

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