Placebo and nocebo effects: from observation to harnessing and clinical application

Tu, Yiheng; Zhang, Libo; Kong, Jian

doi:10.1038/s41398-022-02293-2

Cited by 16 publications

(6 citation statements)

References 142 publications

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“…Since the seminal work of Eisenberger et al (2003 ; for an overview, see Eisenberger (2015) ), many studies reported the activation of part of the affective-motivational component of the pain matrix (i.e., AI and aMCC) when participants experienced or were reminiscent of social pain ( Peyron et al, 2000 ; Eisenberger and Lieberman, 2005 ; Masten et al, 2012 ; Cacioppo et al, 2013 ; Novembre et al, 2015 ; Rotge et al, 2015 ). These regions are those most frequently involved in nociceptive pain elaboration (e.g., Lui et al, 2008 ; for an overview, see Xu et al, 2020 ), including the codification of pain intensity ( Favilla et al, 2014 ), but also in conditions that include pain modulation, observation of painful stimuli, placebo and nocebo, and empathy ( Zaki et al, 2016 ; Zunhammer et al, 2021 ; Tu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain

Borelli,

Benuzzi,

Ballotta

et al. 2023

Front. Neurosci.

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IntroductionRecent studies have shown that processing semantic pain, such as words associated with physical pain, modulates pain perception and enhances activity in regions of the pain matrix. A direct comparison between activations due to noxious stimulation and processing of words conveying physical pain may clarify whether and to what extent the neural substrates of nociceptive pain are shared by semantic pain. Pain is triggered also by experiences of social exclusion, rejection or loss of significant others (the so-called social pain), therefore words expressing social pain may modulate pain perception similarly to what happens with words associated with physical pain. This event-related fMRI study aims to compare the brain activity related to perceiving nociceptive pain and that emerging from processing semantic pain, i.e., words related to either physical or social pain, in order to identify common and distinct neural substrates.MethodsThirty-four healthy women underwent two fMRI sessions each. In the Semantic session, participants were presented with positive words, negative pain-unrelated words, physical pain-related words, and social pain-related words. In the Nociceptive session, participants received cutaneous mechanical stimulations that could be either painful or not. During both sessions, participants were asked to rate the unpleasantness of each stimulus. Linguistic stimuli were also rated in terms of valence, arousal, pain relatedness, and pain intensity, immediately after the Semantic session.ResultsIn the Nociceptive session, the ‘nociceptive stimuli’ vs. ‘non-nociceptive stimuli’ contrast revealed extensive activations in SI, SII, insula, cingulate cortex, thalamus, and dorsolateral prefrontal cortex. In the Semantic session, words associated with social pain, compared to negative pain-unrelated words, showed increased activity in most of the same areas, whereas words associated with physical pain, compared to negative pain-unrelated words, only activated the left supramarginal gyrus and partly the postcentral gyrus.DiscussionOur results confirm that semantic pain partly shares the neural substrates of nociceptive pain. Specifically, social pain-related words activate a wide network of regions, mostly overlapping with those pertaining to the affective-motivational aspects of nociception, whereas physical pain-related words overlap with a small cluster including regions related to the sensory-discriminative aspects of nociception. However, most regions of overlap are differentially activated in different conditions.

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Section: Discussionmentioning

confidence: 99%

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain

Borelli,

Benuzzi,

Ballotta

et al. 2023

Front. Neurosci.

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“…This may occur through multiple pathways that are involved in integrating expectations and sensory information (Geuter et al, 2017). Especially the descending pain modulatory system (DPMS; Geuter et al, 2017; Tu et al, 2022) is associated with placebo and nocebo effects and is thought to consist of areas like the periaqueductal grey (PAG), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and amygdala (Eippert et al, 2009), as well as frontal areas like the vmPFC (Geuter et al, 2017; Tu et al, 2022). Further, placebo and nocebo effects modulate activity in areas classically associated with pain processing like the thalamus and the insula during noxious stimulation (Atlas & Wager, 2014; Wager & Atlas, 2015; Wager et al, 2004; Zunhammer et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

The neural dynamics of positive and negative expectations of pain

Wittkamp,

Wolf,

Rose

2024

Preprint

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Pain is heavily modulated by expectations. Whereas the integration of expectations with sensory information has been examined in some detail, little is known about how positive and negative expectations are generated and their neural dynamics from generation over anticipation to the integration with sensory information. The present preregistered study employed a novel paradigm to induce positive and negative expectations on a trial-by-trial basis and examined the neural mechanisms using combined EEG-fMRI measurements (n=50). We observed substantially different neural representations between the anticipatory and the actual pain period. In the anticipation phase i.e., before the nociceptive input, the insular cortex, dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) showed increased activity for expectations regardless of their valence. Interestingly, a differentiation between positive and negative expectations within the majority of areas only occurred after the arrival of nociceptive information. FMRI-informed EEG analyses could reliably track the temporal sequence of processing showing an early effect in the DLPFC, followed by the anterior insula and late effects in the ACC. The observed effects indicate the involvement of different expectation-related subprocesses, including the transformation of visual information into a value signal that is maintained and differentiated according to its valence only during stimulus processing.

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“…However, even though the relationship between th placebo effect (positive expectations) in clinical interventions was widely investigated, there were not enough studies on negative expectations (nocebo effect). [ 21 ] Accordingly, we attempted to close this research gap by studying the different aspects of negative expectations in clinical interventions and providing materials to improve. The aim of the present study is to investigate the effects of the negative expectations in therapeutic interventions and how negative expectations or in other words the nocebo responses affect the therapeutic results.…”

Section: Introductionmentioning

confidence: 99%

Negative expectations (nocebo phenomenon) in clinical interventions: A scoping review

Nasiri-Dehsorkhi,

Vaziri,

Esmaillzadeh

et al. 2024

Journal of Education and Health Promotion

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Unpredictable, undesirable, and confusing reactions in the face of psychological or medical interventions make the clinical presentation more complicated and may represent clinically unexplained symptoms and also disturbed the doctor–patients relationship and decrease patients’ benefits of treatment. It seems that negative expectations from the treatment (nocebo phenomenon) can explain such reactions. The aim of the current study is a scoping review and investigate different aspects of the nocebo phenomenon (negative expectations) in clinical interventions. This paper follows a scoping review of the existence, importance, and multidimensions of the nocebo phenomenon in medical and psychological interventions. Data sources include literature databases (ProQuest, PubMed, Google Scholar, and Scopus) reviewed from inception dates to 2023, and the terms negative expectations, nocebo effect, placebo effect, negative placebo, and clinical interventions were searched. The review of the available articles showed that negative expectations play an important role in the process and effectiveness of clinical interventions. Negative expectations (here named nocebo effect) can significantly interfere with rapport and treatment processes. Some underlying components of the nocebo effect include negative expectancies, conditioning, social learning, memory, cognitive distortions, meaning, motivation, somatic focus, negative reinforcements, personality, anxiety, and neurophysiological factors such as CCK, dopamine, and cortisol are proposed for development and presence of nocebo phenomenon in clinical practice. Negative expectations with its biopsychosocial aspects play an important and amazing role in disorganizing medical and psychological interventions. Using appropriate methods to reduce nocebo effects in therapeutic interventions may increase treatment compliance and adherence and increase the effectiveness of interventions.

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Placebo and nocebo effects: from observation to harnessing and clinical application

Cited by 16 publications

References 142 publications

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain

Words hurt: common and distinct neural substrates underlying nociceptive and semantic pain

The neural dynamics of positive and negative expectations of pain

Negative expectations (nocebo phenomenon) in clinical interventions: A scoping review

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