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Schematic representation of the experimental protocol.: (a) After a first training session, a conditioning session was performed in which an inert treatment (TENS) was applied together with verbal instructions that it could induce a decrease of force and with a manipulation in which the visual feedback was surreptitiously reduced. After the motor task was completed, subjects were asked to judge TENS efficacy on a VAS ranging from 0 (not effective) to 10 (very effective). Afterwards, the procedure was repeated again in the test session, but this time the (fake) effect of TENS was removed. (b) Example of answers of participants who gave higher scores of TENS efficacy in the test compared to the conditioning session (dark blue, positive Δ TENS effectiveness score), and participants who gave lower scores in the test compared to the conditioning (light blue, negative Δ TENS effectiveness score).
Source publication
The nocebo effect in motor performance consists in a reduction of force and increase of fatigue following the application of an inert treatment that the recipient believes to be effective. This effect is variable across individuals and it is usually stronger if conditioning –exposure to the active effect of the treatment– precedes a test session, i...
Citations
... Personality factors can significantly influence the patients' positive and negative expectations in clinical interventions by presenting placebo and nocebo effects. [27,28] Factors such as optimistic mood, [29] hypnotic suggestibility, [30] bodily focus, [29] empathy, [31,32] neuroticism, altruism, [33] propensity for social relationships, [34] dopamine-related personality trait, [35] anxiety, [36] fear of pain, [37] focus on ego resilience, [38] pessimism, [39] pain catastrophizing, [33] harm avoidance, [39] and persistence [28] are related to placebo and nocebo effects. [28] On the other hand, anxiety, harm avoidance, persistence, and pain catastrophizing [33,40] have been associated with negative expectations and the nocebo effects. ...
... Personality factors can significantly influence the patients' positive and negative expectations in clinical interventions by presenting placebo and nocebo effects. [27,28] Factors such as optimistic mood, [29] hypnotic suggestibility, [30] bodily focus, [29] empathy, [31,32] neuroticism, altruism, [33] propensity for social relationships, [34] dopamine-related personality trait, [35] anxiety, [36] fear of pain, [37] focus on ego resilience, [38] pessimism, [39] pain catastrophizing, [33] harm avoidance, [39] and persistence [28] are related to placebo and nocebo effects. [28] On the other hand, anxiety, harm avoidance, persistence, and pain catastrophizing [33,40] have been associated with negative expectations and the nocebo effects. ...
... While optimism and persistence have a negative correlation with nocebo effects. [39] Research in the field of nocebo effect shows that negative expectations play an important role both psychologically and neurobiologically in the occurrence of nocebo phenomenon. So that, negative expectations by mediating negative emotions such as stress, fear, and anxiety, [1,[41][42][43] and at the neurophysiological level by activating the hypothalamus pituitary adrenal axis (HPA), which acts in response to stress and the accumulation of the stress hormone cortisol. ...
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.
... [15] The nocebo effect is defined as increased pain or other symptoms after administration of an inactive treatment purported to increase pain or unpleasant symptoms, [16,17] or negative outcome following the application of an inert treatment that the recipient believes to be effective. [18][19][20] The underlying of placebo and nocebo effects are psycho-neurobiological. Psychological mechanisms include expectancies, conditioning, learning, memory, motivation, somatic focus, reward, anxiety reduction, and meaning. ...
BACKGROUND: Psychological distress and perceived stress may complicate the clinical presentation, course, and treatment of patients with functional gastrointestinal disorders. The correlation between psychological distress, perceived stress, and the nocebo effect (multifood adverse reaction) in patients with irritable bowel syndrome (IBS) was the main aim of the present study.
MATERIALS AND METHODS: In this cross-sectional correlation study, data on 4,763 Iranian adults, 748 of whom by purposive sampling were patients with IBS (65.1% female), working in 50 different health centers affiliated to the Isfahan University of Medical Sciences across Isfahan province were examined. For assessing dietary intake, a 106-item self-administered Dish-based Semi-Quantitative Food Frequency Questionnaire that was specifically designed and validated for Iranian adults was used. General Heath Questionnaire 12 and Stressful Life event Questionnaire were used to assess psychological distress and perceived stress. By using a modified Persian version of the Rome III questionnaire, IBS was assessed. Based on researcher-made definition of nocebo effect (multiitem food intolerance), 164 people had the nocebo phenomenon in IBS group.
RESULTS: Age, sex, education, marital status, antidepressant use, and specifically chronic underlying disease (odds ratio [OR]: 3.54, 95% confidence interval [CI]: 1.73-7.23) of general characteristics had a significant correlation (P
... We know only one study investigating the role of personality traits in response to placebo and nocebo interventions concerning motor performance. Corsi et al. (2016) found that the magnitude of nocebo response (force production) was associated with lower levels of optimism and higher levels of anxiety. Also, people with higher levels of persistence perceived the negative effect as lower. ...
Placebo and nocebo effects could influence the perceived, actual, or both postural stabilities. Therefore, this experiment examined whether postural stability is susceptible to placebo and nocebo effects. Driven by expectations, these cognitions could influence the motor stability of people in physical rehabilitation and those with motion instability. We randomly assigned 78 participants to a placebo, nocebo, or control group. Then, we applied a sham sports cream with positive, negative, or neutral instructions about its impact on balance. Next, we tested postural stability with a modified version of the Modified Clinical Test of Sensory Interaction in Balance, including standard, proprioceptive, visual, and vestibular tests before and after the intervention. Further, we measured expected and perceived performance with visual analog scales and assessed trait anxiety, change in state anxiety, optimism, holistic thinking, persistence, and cooperation with questionnaires. The intervention did not affect actual test performances; similarly, trait and state variables and expectations did not have an impact. Furthermore, the experimental manipulation and trait and state variables did not significantly affect perceived performance. However, the association between expectation and perceived performance was strong (ϱ = 0.627, p < 0.001). These findings suggest that postural stability is not susceptible to placebo and nocebo influences. Still, there is a dissociation between objective and subjective performance, showing that expectations impact perceived but not actual performance, which could fuel motivation in rehabilitation settings.
Supplementary Information
The online version contains supplementary material available at 10.1186/s41235-023-00476-z.
... In closer alignment with the current research, Zech et al. (2020) showed that negative verbal suggestions (e.g., statements indicating an individual in a clinical setting will experience pain) lead to decreases on objective measures of physical strength; with anxiety seeming to enhance this effect. Similarly, researchers have shown that treatment expectations can impact motor performance, in the form of reduced force and increased fatigue, and that higher anxiety also plays an important role (Corsi et al., 2016). ...
Drug recalls and lawsuits against pharmaceutical manufacturers are accompanied by announcements emphasizing harmful drug side-effects. Those with elevated health anxiety may be more reactive to such announcements. We evaluated whether health anxiety and financial incentives affect subjective symptom endorsement, and objective outcomes of cognitive and physiological functioning during a mock drug recall. Hundred and sixty-one participants reported use of over-the-counter pain medications and presented with a fictitious medication recall via a mock Food and Drug Administration (FDA) website. The opportunity to join a class-action lawsuit was manipulated. We assessed health anxiety, recalled drug usage, blood pressure, heart rate, and performance on a computerized Trail Making Test (TMT). Symptom endorsement was strongly predicted by health anxiety. When combined, three health anxiety measures explained 28.5% variance (Cohen’s d = 1.26). These effects remain strong after controlling for depression and anxiety. Litigation condition did not predict symptom endorsement. Blood pressure and heart rate were modestly predicted by health anxiety, but not by litigation condition. TMT performance was consistently predicted by health anxiety, with higher scores associated with poorer performance. Although there were no main effects for litigation, interactions consistently emerged for the TMT, with generally poorer performance for those with higher health anxiety in the non-litigation condition; whereas health anxiety was unrelated to performance for the litigation condition. All but one participant joined the litigation when given the opportunity, despite a healthy sample and minimal use of pain medication. Subsequent data from 67 individuals with no mention of the FDA scenario or litigation showed that health anxiety still significantly predicts symptom endorsement (12.6% variance), but the explained variance is less than half that obtained in the FDA scenario. The findings suggest that health anxiety plays a significant role in adverse symptom reporting, beyond anxiety or depression, and this effect is independent of the presence of the FDA recall. The lack of differences for health anxiety and symptom endorsement between litigation and non-litigation conditions rules out malingering. Although it is general practice in drug recalls to list potential adverse side effects caused by medications, this may elicit unintended symptom experiences and health anxious individuals may be more susceptible.
... Compared to the placebo effect, less research has investigated psychological traits associated with nocebo responsiveness (23). However, traits such as high state and trait anxiety [assessed with state-trait anxiety inventory in Camerone et al. (15), Colloca et al. (24), and Corsi et al. (25)], fear of pain [assessed with the Fear of Pain Questionnaire in Aslaksen and Lyby (26)] and low optimism [assessed with the revised life oriented test in Geers et al. (27)] have been associated with greater nocebo responsiveness. In addition, high anxiety has been shown to be a predictor of enhanced pain perception [assessed with the Beck Anxiety Inventory in Kose-Ozlece et al. (28)]. ...
... However, similarly to other recently published research (47,48), we did not find a correlation between optimism/pessimism and nocebo responsiveness. For what concerns anxiety, most of the studies reporting a correlation, assessed anxiety with the state-trait anxiety inventory [e.g., Camerone et al. (15); Corsi et al. (25) found a correlation with trait anxiety; Colloca et al. (24) showed a correlation with both state and trait anxiety], while in the present study, we measured anxiety with the BAI, as done in the study of Kose-Ozlece et al. (28), in which a correlation between high anxiety and enhanced pain perception was reported. Therefore, the lack of correlation could be due to the assessment of anxiety with the BAI rather than with the state-trait anxiety inventory. ...
Background
The direction and the magnitude of verbal suggestions have been shown to be strong modulators of nocebo hyperalgesia, while little attention has been given to the role of their temporal content. Here, we investigate whether temporal suggestions modulate the timing of nocebo hyperalgesia in an experimental model of sustained pain.
Methods
Fifty-one healthy participants were allocated to one of three groups. Participants received an inert cream and were instructed that the agent had either hyperalgesic properties setting in after 5 (Nocebo 5, N5) or 30 (Nocebo 30, N30) minutes from cream application, or hydrating properties (No Expectation Group, NE). Pain was induced by the Cold Pressure Test (CPT) which was repeated before cream application (baseline) and after 10 (Test10) and 35 (Test35) minutes. Changes in pain tolerance and in HR at each test point in respect to baseline were compared between the three groups.
Results
Tolerance change at Test 10 (Δ10) was greater in N5 (MED = −36.8; IQR = 20.9) compared to NE (MED = −5.3; IQR = 22.4; p < 0.001) and N30 (MED = 0.0; IQR = 23.1; p < 0.001), showing that hyperalgesia was only present in the group that expected the effect of the cream to set in early. Tolerance change at Test 35 (Δ35) was greater in N5 (MED = −36.3; IQR = 35.3; p = 0.002) and in N30 (MED = −33.3; IQR = 34.8; p = 0.009) compared to NE, indicating delayed onset of hyperalgesia in N30, and sustained hyperalgesia in N5. No group differences were found for HR.
Conclusions
Our study demonstrated that temporal expectations shift nocebo response onset in a model of sustained pain.
... Among others, psychological traits and affective states can contribute to placebo and nocebo responsiveness (Colagiuri et al., 2015;Hall et al., 2015;Anderson and Stebbins, 2020;Frisaldi et al., 2020). With regard to these interindividual differences, optimism appears to most consistently contribute to placebo responding in pain (Geers et al., 2005(Geers et al., , 2007(Geers et al., , 2010; Morton et al., 2009;Darragh et al., 2014;Corsi et al., 2016), whereas anxiety seems to play a role in eliciting nocebo effects in particular (Aslaksen and Lyby, 2015;Corsi et al., 2016;Kern et al., 2020;Thomaidou et al., 2021). The evidence for the contribution of other interindividual differences, including those in personality traits of the Big Five model (i.e., neuroticism, extraversion, openness to experience, conscientiousness, agreeableness), (disposition to) worrying, or Abbreviations: BAS, Behavioral Activation System; BIS, Behavioral Inhibition System; NRS, Numeric Rating Scale; VSs, verbal suggestions. ...
... Among others, psychological traits and affective states can contribute to placebo and nocebo responsiveness (Colagiuri et al., 2015;Hall et al., 2015;Anderson and Stebbins, 2020;Frisaldi et al., 2020). With regard to these interindividual differences, optimism appears to most consistently contribute to placebo responding in pain (Geers et al., 2005(Geers et al., , 2007(Geers et al., , 2010; Morton et al., 2009;Darragh et al., 2014;Corsi et al., 2016), whereas anxiety seems to play a role in eliciting nocebo effects in particular (Aslaksen and Lyby, 2015;Corsi et al., 2016;Kern et al., 2020;Thomaidou et al., 2021). The evidence for the contribution of other interindividual differences, including those in personality traits of the Big Five model (i.e., neuroticism, extraversion, openness to experience, conscientiousness, agreeableness), (disposition to) worrying, or Abbreviations: BAS, Behavioral Activation System; BIS, Behavioral Inhibition System; NRS, Numeric Rating Scale; VSs, verbal suggestions. ...
... Although some direct moderation effects were found in the current work, for instance of traits and suggestions on expectations, these were not actually associated with itch experience. This is in line with studies that show that these traits do not predict placebo or nocebo responses (Corsi and Colloca, 2017;Gillving et al., 2020;Kern et al., 2020), but contradicts several studies that do report such associations (e.g., that optimism can predict placebo responding: see Geers et al., 2005Geers et al., , 2007Geers et al., , 2010Morton et al., 2009;Darragh et al., 2014;Corsi et al., 2016;Zhou et al., 2019). These discrepancies between study findings may be attributable to differences in methodology, or to differences in the type of symptoms that were assessed (i.e., pain versus itch). ...
Introduction: Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent.
Methods: The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; n = 92) or negative VSs (Studies 2+3; n = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses.
Results: The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower.
Conclusion: Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.
... Механизмы, ответственные за действие ноцебо, как и в случае c плацебо, иногда реализуются без осознания пусковых сигналов [13]. Хотя ноцебо-эффект может проявиться у любого пациента, отдельные группы, такие как женщины и лица с тревожными расстройствами, к нему наиболее восприимчивы [25]. ...
The term placebo is defined as a substance with no therapeutic effect that improves health by convincing the patient that the substance is effective. The term comes from the Latin “placere”, meaning “I will delight” or “do good”. Placebo is a universal tool for evaluating non-medical effects in randomized controlled trials to determine the true pharmacological effect of a drug. Examples of placebo action can be found in any field of medicine, but there is no conceptual basis that integrates it into everyday clinical practice, nor is there a corresponding medical education programme. Three main mechanisms of placebo effect are considered: the expectation model, reflective causality and the neurotransmitter model; it is necessary to take into account that these hypotheses may complement each other.Nocebo is defined as a substance that has no therapeutic effect, but worsens the condition of the person receiving it because of the negative beliefs and expectations of the person. Nocebo effect, according to several studies, can be modulated by cholecystokinin. There is evidence that cholecystokininin induces hyperalgesia, “turning” anxiety into pain. According to the negative expectation model, nocebo induces hypothalamic-pituitary-adrenal axis, which increases plasma concentrations of adrenocorticotropic hormone and cortisol. Interest in nocebo has increased in recent years due to the introduction of immunobiological biosimilars in clinical practice. There are reports of a higher frequency of drug withdrawal by patients switching from original drugs to biosimilars in open trials compared to blind ones, suggesting a nocebo effect. The conceptual basis of personalized psychopharmacotherapy is to maximize placebo effect and minimize nocebo effect in order to improve treatment outcomes.
... After the removal of duplicates and the subsequent screening of titles and abstracts of 407 references, we included 40 references for full text evaluation. In total, 24 studies met our inclusion criteria [29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. All of the studies examined healthy subjects except for three studies. ...
... The 24 studies included 14 randomised trials and 10 cohort studies. In terms of interventions, 12 studies used a placebo intervention (( [29][30][31][32][33][35][36][37][38][39][40][41], 5 used a nocebo intervention ( [42][43][44][45][46]), and 7 studies used both ( [47][48][49][50][51][52][53]). Moreover, 14 studies investigated the effect of personality on the placebo/nocebo response based on interaction, and 10 studies investigated the effect based on main effect. ...
... Another study [47] showed no effect of conscientiousness on either response. Nevertheless, one study [29] found that high levels of conscientiousness were negatively correlated with physical performance in the placebo condition, and Corsi and colleagues [43] found that persistence was negatively correlated with the nocebo response. ...
Objective: Some people might be more prone to placebo and nocebo responses than others depending on their personality traits. We aimed to provide a systematic review on the influence of personality traits on placebo and nocebo responses in controlled and uncontrolled studies. Methods: We conducted a systematic literature search in the databases CINAHL, AMED, PsycINFO and EMBASE for relevant publications published between January 1997 and March 2018. For all included papers, we conducted an additional forward search. Results: After screening 407 references, we identified 24 studies. The Big Five (i.e., neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) and optimism were the most frequently investigated personality traits. Several studies found a positive association between optimism and the placebo response. Furthermore, we found that higher anxiety was associated with increased nocebo responses. Conclusion: Evidence points to a possible association between optimism and the placebo response. Therefore, further emphasising the investigation of the influence of optimism on the placebo/nocebo response seems warranted. For clinical practice, the impact of anxiety on the nocebo response might be important to identify patients who might be more prone to experiencing side effects of medical treatments.
... Although all patients may be susceptible to nocebo effects, certain subgroups may be at particular risk, including women and individuals with psychological disorders such as anxiety (Klosterhalfen et al., 2009;Wells and Kaptchuk, 2012;Data-Franco and Berk, 2013;Corsi et al., 2016;Corsi and Colloca, 2017;Vambheim and Flaten, 2017). The interaction of these factors may explain large variations in nocebo effects seen among individuals . ...
Nocebo effects encompass negative responses to inert interventions in the research setting and negative outcomes with active treatments in the clinical research or practice settings, including new or worsening symptoms and adverse events, stemming from patients’ negative expectations and not the pharmacologic action of the treatment itself. Numerous personality, psychosocial, neurobiological, and contextual/environmental factors contribute to the development of nocebo effects, which can impair quality of life and reduce adherence to treatment. Biologics are effective agents widely used in autoimmune disease, but their high cost may limit access for patients. Biosimilar products have gained regulatory approval based on quality, safety, and efficacy comparable to that of originator biologics in rigorous study programs. In this review, we identified gaps in patients’ and healthcare professionals’ awareness, understanding, and perceptions of biosimilars that may result in negative expectations and nocebo effects, and may diminish their acceptance and clinical benefits. We also examined features of nocebo effects with biosimilar treatment that inform research and clinical practices. Namely, when biosimilars are introduced to patients as possible treatment options, we recommend adoption of nocebo-reducing strategies to avoid negative expectations, including delivery of balanced information on risk–benefit profiles, framing information to focus on positive attributes, and promoting shared decision-making processes along with patient empowerment. Healthcare professionals confident in their knowledge of biosimilars and aware of bias-inducing factors may help reduce the risk of nocebo effects and improve patients’ adherence in proposing biosimilars as treatment for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.
... After the removal of duplicates and the subsequent screening of titles and abstracts of 407 references, we included 40 references for full text evaluation. In total, 24 studies met our inclusion criteria [29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. All of the studies examined healthy subjects except for three studies. ...
... The 24 studies included 14 randomised trials and 10 cohort studies. In terms of interventions, 12 studies used a placebo intervention (( [29][30][31][32][33][35][36][37][38][39][40][41], 5 used a nocebo intervention ( [42][43][44][45][46]), and 7 studies used both ( [47][48][49][50][51][52][53]). Moreover, 14 studies investigated the effect of personality on the placebo/nocebo response based on interaction, and 10 studies investigated the effect based on main effect. ...
... Another study [47] showed no effect of conscientiousness on either response. Nevertheless, one study [29] found that high levels of conscientiousness were negatively correlated with physical performance in the placebo condition, and Corsi and colleagues [43] found that persistence was negatively correlated with the nocebo response. ...
Objective:
Some people might be more prone to placebo and nocebo responses than others depending on their personality traits. We aimed to provide a systematic review on the influence of personality traits on placebo and nocebo responses in controlled and uncontrolled studies.
Methods:
We conducted a systematic literature search in the databases CINAHL, AMED, PsycINFO and EMBASE for relevant publications published between January 1997 and March 2018. For all included papers, we conducted an additional forward search.
Results:
After screening 407 references, we identified 24 studies. The Big Five (i.e., neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) and optimism were the most frequently investigated personality traits. Several studies found a positive association between optimism and the placebo response. Furthermore, we found that higher anxiety was associated with increased nocebo responses.
Conclusion:
Evidence points to a possible association between optimism and the placebo response. Therefore, further emphasising the investigation of the influence of optimism on the placebo/nocebo response seems warranted. For clinical practice, the impact of anxiety on the nocebo response might be important to identify patients who might be more prone to experiencing side effects of medical treatments.
