Corrigendum: Nocebo effects in systemic therapies for adult plaque psoriasis: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fmed.2024.1373520.].

Optimizing placebo and minimizing nocebo effects through communication: e-learning and virtual reality training development.

BACKGROUND: The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients' expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands. METHODS: The development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases. RESULTS: Placebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0-10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0-10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future. CONCLUSIONS: We have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.

Assessing the longevity of attribute framing in attenuating the nocebo effect to brand and generic medication.

The perception of taking a generic, relative to brand, medication has been demonstrated to exacerbate the nocebo effect. Conversely, positive attribute framing has been shown to attenuate the nocebo effect. However, little is known about the longevity of positive attribute framing nor how it interacts with generic versus brand treatment cues. Healthy participants (N = 205) were randomised to receive either sham-modafinil capsules with a brand or generic appearance, in conjunction with standard negative side effect framing (brand-negative: N = 42; generic-negative: N = 41) or positive side effect framing (brand-positive: N = 40; generic-positive: N = 40). The remainder were randomised to a no-treatment control (N = 42). Participants were informed that modafinil could enhance alertness and cognitive performance and reduce fatigue. Critically, modafinil was described as having several potential side effects. Treatment-related side effects, alertness, fatigue and cognitive performance were measured at baseline, 30-min post-treatment and 24 h later. Nocebo and placebo effects were observed across modafinil-treated participants relative to control. Positive framing significantly reduced warned side effects for 24 h. Perceived side effect likelihood, severity, and worry mediated the nocebo, but not framing, effect. Results have important implications for the presentation of side effect information, providing a potential route to reduce unwanted negative effects of generic medication.

¿Influye la comunicación con el paciente sobre la kinesiofobia? Una revisión sistemática / Does patient communication influence kinesiophobia? A systematic review

El objetivo de la presente revisión sistemática consistió en determinar el efecto de la comunicación en el ámbito sanitario sobre la kinesiofobia. Para ello, se realizó una búsqueda bibliográfica en siete bases de datos entre noviembre de 2022 y febrero de 2023. La revisión se efectuó acorde a la declaración Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) y para el análisis de la calidad metodológica se utilizaron: la escala Physiotherapy Evidence Database (PEDro), los criterios de Van Tulder y el análisis del riesgo de sesgo de la Colaboración Cochrane. Se incluyeron un total de 13 artículos que presentaron una calidad metodológica media de 7,1 sobre 10. Se obtuvieron resultados significativos para al menos una variable (kinesiofobia, discapacidad o nivel de actividad física) en 12 trabajos. Existe evidencia sólida de que la comunicación puede influir sobre la kinesiofobia del sujeto. Es más probable que esta influencia ocurra en un sentido negativo o discapacitante, pero también puede actuar en sentido positivo disminuyendo la misma. (AU)

The aim of the present systematic review was to determine the effect of communication in the health care setting on kinesiophobia. To this end, a literature search was conducted in seven databases between November 2022 and February 2023. The review was carried out following the PRISMA statement and for the analysis of methodological quality we used: PEDro Scale, Van Tulder criteria and risk of bias analysis of the Cochrane Collaboration. A total of 13 articles were included with a mean methodological quality of 7.1 out of 10. Significant results were obtained for at least one variable (kinesiophobia, disability or level of physical activity) in 12 articles. There is strong evidence that communication can influence a subject's kinesiophobia. This influence is most likely to be in a negative or disabling sense, but it can also act in a positive sense by decreasing it. (AU)

Social Learning of Placebo Effects in Pain: A Critical Review of the Literature and a Proposed Revised Model.

Relatively recently, in 2009, experimental studies were undertaken to determine the role of social observational learning in forming hypoalgesic, analgesic and hyperalgesic responses to a placebo. The research findings obtained in studies published before 2018 were integrated and formed the basis of the theoretical model of social learning of placebo effects in pain proposed by Bajcar and Babel. This model considered the involvement of different types of modeling (ie, behavioral modeling, symbolic modeling, and verbal modeling) in shaping placebo hypoalgesia/analgesia and nocebo hyperalgesia. The model assumed that pain expectancies might be involved in observationally induced placebo effects in pain and that the effectiveness of observational learning in shaping placebo effects could be moderated by the observer's dispositions, especially empathy. Based on the latest research data, we propose a modified and significantly extended version of this model. The revised model includes the involvement of particular types of modeling in placebo effects and their role in shaping conscious pain-related expectancies. It explains the role of dispositional empathy in shaping observationally induced placebo effects. Notably, the extended version of the model considers the contribution of the characteristics of the observed person to the magnitude of placebo effects induced by social learning. PERSPECTIVE: The paper proposes a comprehensive theoretical approach to explaining the role of observational learning in shaping placebo effects in pain. The proposed model emphasizes the potential of this form of learning in shaping placebo responses and indicates factors that can modify the effectiveness of observational learning.

Exploratory study of nocebo effect in senior medical students.

Background: Νocebo Effect is known to induce adverse symptoms after negative expectations which can be manifested on a physical and psychological level. As 6th year medical students often face a wide range of clinical challenges and may be prone to negative expectations or beliefs affecting their pre-clinical and clinical success, we want to investigate how they are affected by the Nocebo Effect. Objective: To investigate whether a nocebo effect can be induced when exposing final-year students to the clinical context of their training. Methods: We used verbal suggestions as a nocebo mechanism and by using three tools, the Illness Attitude Scales, the Symptom Checklist-90, and the State-Trait Anxiety Inventory, we examined the difference in scores on measures of psychometric parameters in 33 participants who were on their 6th year medical and attended three clinics for the first time during their education. The administrations were given before and after attending each clinic, and negative verbal suggestions were given prior to the first administration. We also measured whether the overall number of clinics, had an effect on psychometric parameters. Results: The results revealed a significant increase in second administration overall in the three clinics in specific psychometric parameters but no statistically significant difference was observed after attending consecutive clinics. Conclusion: Students reported the occurrence of adverse symptoms in the investigated psychometric parameters, which should be noted in order to avoid potential educational clinical failure.

Learning by observing: a systematic exploration of modulatory factors and the impact of observationally induced placebo and nocebo effects on treatment outcomes.

Introduction: Observational learning (OL) refers to learning through observing other people's behavior. OL has been suggested as an effective and simple tool to evoke treatment expectations and corresponding placebo and nocebo effects. However, the exact mechanisms by which OL shapes treatment outcomes, its moderating factors and possible areas of application remain unclear. We thus reviewed the existing literature with two different literature searches to answer the following questions: Which influencing factors contribute to OL-induced placebo and nocebo effects (in healthy volunteers and patients) and how large are these effects (search 1)? In which medical fields has OL been used so far to modulate treatment expectancy and treatment outcomes in patients, their caregivers, and at-risk groups (search 2)? We also aimed to explore whether and how the assessment of treatment expectations has been incorporated. Methods: We conducted two independent and comprehensive systematic literature searches, both carried out on September 20, 2022. Results: We identified 21 studies that investigated OL-mediated placebo and nocebo effects for pain and itch, the (placebo) efficacy of sham treatment on anxiety, and the (nocebo) induction of medication side effects (search 1). Studies showed that OL can efficiently induce placebo and nocebo effects across different presentation modes, with medium effect sizes on average: placebo effects, d = 0.79 (range: d = -0.36-1.58), nocebo effects, d = 0.61 (range: d = 0.04-1.5). Although several moderating factors have been investigated, their contribution to OL-induced effects remains unclear because of inconsistent results. Treatment expectation was assessed in only four studies. Regarding medical applications of OL (search 2), we found 12 studies. They showed that OL was effectively applied in preventive, therapeutic and rehabilitative interventions and that it was mainly used in the field of psychosomatics. Discussion: OL effects on treatment outcomes can be both positive and negative. Future research should investigate which individuals would benefit most from OL and how OL can be implemented most effectively to induce placebo and avoid nocebo effects in clinical settings. Systematic review registration: This work was preregistered at the Center for Open Science as open-ended registration (doi: 10.17605/OSF.IO/FVHKE). The protocol can be found here: https://archive.org/details/osf-registrations-fvhke-v1.

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

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.

Nocebo effects in systemic therapies for adult plaque psoriasis: A systematic review and meta-analysis.

Introduction: The nocebo effect is defined as adverse outcomes secondary to negative patient expectations rather than the pharmacologic activity of an intervention. Nocebo effects can reduce treatment adherence and/or persistence. Therefore, nocebo effects in psoriasis need to be defined. Methods: A Cochrane systematic review was updated with a search of MEDLINE, Embase, and the CENTRAL Register of Controlled Trials for phase II - IV RCTs comparing systemic therapy versus placebo for patients with moderate-to-severe plaque psoriasis. Estimates were pooled using a random effects model, and heterogeneity was evaluated using the I2 statistic. The primary outcome was the pooled proportion of any adverse event (AE) and corresponding risk difference (RD) in patients randomized to placebo versus systemic therapy. Results: A total of 103 unique trials were identified enrolling 43,189 patients. The overall pooled AE rate in patients randomized to systemic therapy was 57.1% [95% CI: 54.7-59.5%] compared to 49.8% [95% CI: 47.1-52.4%] for placebo [RD 6.7% (95% CI: 4.6-8.9%), p < 0.00001, I2 = 75%]. Both biologic and non-biologic systemic therapy groups had a higher proportion of infectious AEs compared to placebo. No statistically significant RD in serious AEs or AEs leading to discontinuation was identified between systemic therapy and placebo groups. Discussion: Half of patients exposed to inert placebo in clinical trials of systemic psoriasis therapies experienced AEs, which may be explained by nocebo effects. These findings have important implications when counseling patients and designing future studies.

[Does patient communication influence kinesiophobia? A systematic review]. / ¿Influye la comunicación con el paciente sobre la kinesiofobia? Una revisión sistemática.

The aim of the present systematic review was to determine the effect of communication in the health care setting on kinesiophobia. To this end, a literature search was conducted in seven databases between November 2022 and February 2023. The review was carried out following the PRISMA statement and for the analysis of methodological quality we used: PEDro Scale, Van Tulder criteria and risk of bias analysis of the Cochrane Collaboration. A total of 13 articles were included with a mean methodological quality of 7.1 out of 10. Significant results were obtained for at least one variable (kinesiophobia, disability or level of physical activity) in 12 articles. There is strong evidence that communication can influence a subject's kinesiophobia. This influence is most likely to be in a negative or disabling sense, but it can also act in a positive sense by decreasing it.

Non adherence to lipid-lowering therapy and strategies to improve adherence.

Lipid lowering therapies is well-established to prevent cardiovascular events in adults with dyslipidemia and multiple risk factors. However, global clinical usage of LLT,particularly statins remains suboptimal, with adherence low rates for primary prevention and secondary prevention. Low adherence is influenced by concerns about side effects, misconceptions about benefits. Patients often discontinue statins due to perceived side effects, despite clinical trials showing no increase in symptoms compared to placebo. Poor understanding of statin benefits, doubts about their necessity, and suspicions of over prescription contribute to nonadherence, which is often amplified by negative portrayal of LLT specialy statins on social media. Strategies to improve adherence include addressing patient concerns, enhancing physician-patient communication, and increasing patient education. Optimizing statin usage and reducing the burden of cardiovascular disease necessitates addressing patient perceptions and improving communication between healthcare providers and patients.

Patient-reported muscle symptoms and their characterization in a hypertensive population eligible for statin therapy: An exploratory study.

BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) are claimed to be frequent in clinical practice. We evaluated the prevalence and characteristics of patient-reported muscle symptoms (PRMS) attributed to drugs/nutraceuticals in hypertensive patients, focusing the attention on statin treatment. METHODS AND RESULTS: Observational study on 390 consecutive outpatients. All patients were asked the following question: "Have you ever taken a drug/nutraceutical that you think gave you muscle symptoms?". Patients who answered "yes" were evaluated with a modified version of the SAMS-clinical index (SAMS-CI). Mean age: 60.5 ± 13.5 years (males 53.8%.). Patients who have ever taken a statin: 250. Patients who have never taken a statin: 140. Prevalence of PRMS (48.5% of the entire study population) did not differ between groups (p = 0.217). Only age, followed by number of drugs taken, was significantly associated with PRMS at multivariate analysis. A high prevalence of low scores to all the questions of "modified" SAMS-CI was found in both groups. Localization and pattern of PRMS did not differ between groups (p = 0.170). Timing of PRMS onset after starting the drug (p = 0.036) and timing of improvement after withdrawal (p = 0.002) were associated with statin therapy. CONCLUSION: PRMS are highly prevalent among the hypertensive population and are believed to be drug-related, especially with aging and regardless of whether the drug taken is a statin or not. These findings are in line with the growing evidence that subjective muscle symptoms are often misattributed to statins, while they may more likely be related to the nocebo/drucebo effect or to other common undiagnosed conditions.

Association Between Electronic Device Use at Bedtime and COVID-19 Vaccine-Related Adverse Events During the COVID-19 Pandemic in Korean Adults: A Nationwide Cross-Sectional Population-Based Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to heightened mood disturbances linked to increased electronic device use at bedtime (EUB). General anxiety may contribute to an increased likelihood of experiencing nocebo responses, which have been reported to be associated with COVID-19 vaccine-related adverse events (CAEs). However, no related studies have been conducted to examine this association to date. METHODS: We executed a nationwide cross-sectional study to explore these correlations during the pandemic. Using data from the 2022 National Sleep Survey of South Korea, we analyzed the sleep health of 4,000 adults aged 20-69 years between January and February 2022. Shift workers and those with severe sleep disorders were excluded. Participants with EUB more than four days a week were labeled as high frequency EUB, and those reporting CAEs after both vaccine doses were marked as having a presence of CAEs. The survey also included details about anthropometric data, socioeconomic status, and sleep status. RESULTS: Of the 3,702 participants, 92.6% had received two or more vaccine doses, with 41.2% experiencing CAEs. Furthermore, 73.7% had a high EUB frequency. Factors associated with CAE reporting included younger age, female sex, and high EUB frequency, while heavy alcohol use was found to be less likely to be associated with CAE reporting. Notably, a high EUB frequency was significantly associated with reported CAEs (odds ratio, 1.223; 95% confidence interval, 1.028-1.455; P = 0.023). CONCLUSION: A nationwide online survey conducted in South Korea during the pandemic found that individuals who engaged in the relatively frequent use of electronic devices during bedtime had worse sleep quality and increased COVID-19-related adverse events compared with those using these devices less frequently. These findings have the potential to enhance our understanding of the impact of the use of electronic devices at bedtime on health.

Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) for non-epileptic seizures: a consecutive case series.

BACKGROUND: Research has demonstrated that implementation of Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) achieved full symptom remission in 93% of people with Functional Neurological Symptoms Disorder (FNSD), most of them exhibiting motor symptoms. The basis for NH-CBT is consistent with a predictive coding aetiological model of FNSD. This idea is transparently shared with people with FNSD in the form of telling them that their symptoms are caused by a nocebo effect, usually followed by some physical activity that aims to change the person's belief about their body. AIMS: To demonstrate that a version of NH-CBT can also be effective in eliminating or reducing non-epileptic seizures (assumed to be a sub-type of FNSD). METHOD: A consecutive case series design was employed. Participants were treated with NH-CBT over a 12-week period. The primary outcome measure was seizure frequency. Numerous secondary measures were employed, as well as a brief qualitative interview to explore participants' subjective experience of treatment. RESULTS: Seven out of the 10 participants became seizure free at least 2 weeks before their post-treatment assessment, and all stayed seizure-free for at least 5 months. Six of those seven remained seizure free at 6-month follow-up. There were large positive effect sizes for the majority of secondary measures assessed. CONCLUSIONS: This case series provides evidence of feasibility and likely utility of NH-CBT in reducing the frequency of non-epileptic seizures.

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study 'NoVis'.

The role of psychological factors in the pathophysiology and treatment of chronic visceral pain in disorders of gut-brain interactions (DGBI) is increasingly appreciated. Placebo research has underscored that expectations arising from the psychosocial treatment context and from prior experiences shape treatment responses. However, effects of negative expectations, i.e., nocebo effects, as they are likely crucial elements of DGBI patients' clinical reality, have thus far only rarely been investigated in the context of visceral pain, with untapped potential for improved prevention and treatment. The experimental randomized-controlled pain study "NoVis," carried out within the Collaborative Research Center (CRC) 289 ("Treatment Expectation"), aims to close gaps regarding the generation and persistence of nocebo effects in healthy volunteers. It is designed to elucidate effects of negative expectations in a multiple-threat paradigm with intensity-matched rectal distensions and cutaneous thermal stimuli, allowing to test nocebo effects in the visceral and somatic pain modalities. Negative expectations are experimentally induced by elements of doctor-patient communication (i.e., instruction) and/or by surreptitious amplification of symptom intensity (i.e., experience/learning) within a treatment context. Accordingly, the repeated measures between-subject design contains the between-group factors "treatment instruction" (negative vs. control) and "treatment experience" (negative vs. control), with volunteers randomized into four experimental groups undergoing several pain stimulation phases (repeated factor). This allows to compare the efficacy of instruction vs. experience, and more importantly, their combined effects on the magnitude of negative expectations and their impact on pain responses, which we expect will be greatest for the visceral modality. After a Baseline, short-term effects are assessed during a test phase accomplished on study day 1 (Test-1 Phase). To explore the persistence of effects, a second test phase is accomplished 1 week later (Test-2 Phase). Effects of negative expectations within and across pain modalities are assessed at the subjective and objective levels, with a focus on psychophysiological and neuroendocrine measures related to stress, fear, and anxiety. Since nocebo effects can play a considerable role in the generation, maintenance, or worsening of chronic visceral pain, and may even constitute risk factors for treatment failure, knowledge from experimental nocebo research has potential to improve treatment outcomes in DGBI and other clinical conditions associated with chronic visceral pain.

Practitioner warmth and empathy attenuates the nocebo effect and enhances the placebo effect.

Augmented patient-practitioner interactions that enhance therapeutic alliance can increase the placebo effect to sham treatment. Little is known, however, about the effect of these interactions on maladaptive health outcomes (i.e., the nocebo effect). Healthy participants (N = 84) were randomised to a 3-day course of Oxytocin nasal drops (actually, sham treatment) in conjunction with a high-warmth interaction (Oxy-HW: N = 28), a low-warmth interaction (Oxy-LW: N = 28) or to a no treatment control group (NT: N = 28). All participants were informed that the Oxytocin treatment could increase psychological well-being but was associated with several potential side effects. Treatment-related side effects, unwarned symptoms, and psychological well-being were measured at baseline and all post-treatment days. Side effect reporting was increased in the Oxy-LW condition compared to the other groups across all days. Conversely, increased psychological well-being was observed in the Oxy-HW condition, relative to the other conditions, but only on Day 1. Among those receiving treatment, positive and negative expectations, and treatment-related worry, did not vary by interaction-style, while psychological well-being and side effect reporting were inversely associated at the level of the individual. Results have important implications for practice, suggesting poorer quality interactions may not only reduce beneficial health outcomes but also exacerbate those that are maladaptive.

Psychological distress, perceived stress and nocebo effect (multifood adverse reaction) in irritable bowel syndrome patients.

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 <.05) with presenting nocebo responses in IBS patients. Psychological distress (OR: 1.415; 95% CI: 0.992-2.020; P = 0.056) had a significant correlation with nocebo effect and did not find significant correlation with perceived stress (OR: 0.999; 95% CI: 0.990-1.008; P = 0.865). Data were analyzed by Chi-square test, analysis of variance, and OR. CONCLUSION: The present study showed that psychological distress with chronic underlying disease and antidepressant use are important elements in presenting multifood adverse reactions that we named here as the nocebo effect in IBS patients. Reducing psychological distress and managing chronic underlying diseases appear to be an effective factor in reducing the nocebo phenomenon in IBS patients. For managing the nocebo responses in IBS patients, these findings may help clinicians to improve their interventions. Further studies are required to confirm these findings.

Placebo hypoalgesic and nocebo hyperalgesic effects in post-extraction patients-A cross sectional study.

Background and objectives: Pain is an unpleasant sensory and emotional experience that affects people's physical, mental, and social health. Patients at times present with postoperative pain with no clinical signs after the surgical dental procedures and adequate pharmacological management. This can be due to the amplified emotional component of the individual in their postoperative period. Hence, this study aimed to estimate the association between placebo, nocebo effects, and postoperative pain associated with tooth extraction procedures. Methods: A cross-sectional study was conducted among 301 patients attending the Department of Oral and Maxillofacial Surgery for tooth extraction. Preoperatively, the expected postoperative pain score was recorded using the "Numerical Rating Scale" (NRS), Anxiety and Depression were assessed using the "Hospital Anxiety and Depression Scale" (HADS), and Patients' expectancy regarding the treatment outcome was assessed using the "Credibility Expectancy Questionnaire" (CEQ). Observed postoperative pain scores at the 6th hour, 24th hour, and peak pain score of the day were recorded using the NRS. Results: There were statistically significant associations (p < 0.05) found between expected and observed postoperative pain, preoperative anxiety and observed postoperative pain, preoperative depression and observed postoperative pain, placebo, nocebo effects, and observed postoperative pain. Interpretation and conclusion: Our study showed a strong association between these variables suggesting that post-extraction pain is a multifaceted condition wherein pain expectation, preoperative anxiety, depression, and expectancy regarding the treatment outcome should be scrutinized before the extraction procedure.

Conditioning induced placebo-like and nocebo-like effects of thermal discomfort in adults but not in youth.

Introduction: Conditioning can be used to modulate the perception of pain, in the form of placebo and nocebo effects. Previous studies show inconsistent results as to whether adolescents show similar, weaker, or non-significant conditioned placebo and nocebo effects compared to effects found in adults. There are suggestions that such differences (if any) may dependent on the cues used in the thermal conditioning paradigms. Therefore, in this current study, we utilized novel, neutral 3D-shaped visual cues to implicitly induce conditioned placebo-like and nocebo-like effects in adolescents and adults. Methods: During the conditioning paradigm, distinct cues (Fribbles) were paired with low and high temperatures in 24 adults and 20 adolescents (mean age = 25.5 years). In the testing phase, these conditioned cues as well as a neutral (unconditioned) cue were presented with moderate temperatures. Results: Thermal discomfort of moderate temperatures was lower when presented with the conditioned low heat cue (placebo-like effect) and higher when thermal stimuli were presented with the high heat cue (nocebo-like effect) compared to the neutral cue. The effects were driven by adults, as neither the placebo-like nor the nocebo-like effect was significant in adolescents. The difference between adolescents and adults was not explained by differences in temperature or discomfort levels, as adults and adolescents had comparable calibrated temperatures and levels of discomfort during heat stimuli. Conclusion: Our findings suggest that thermal perception in adolescents is less influenced by conditioning to an engaging novel visual cue, compared to adults. Our work may have implications for better understanding the scope and limitations of conditioning as a key mechanism of placebo and nocebo effects in youth.