A test of pre-exposure spacing and multiple context pre-exposure on the mechanisms of latent inhibition of dental fear: A study protocol.

BACKGROUND: Latent inhibition occurs when exposure to a stimulus prior its direct associative conditioning impairs learning. Results from naturalistic studies suggest that latent inhibition disrupts the learning of dental fear from aversive associative conditioning and thereby reduces the development of dental phobia. Although theory suggests latent inhibition occurs because pre-exposure changes the expected relevance and attention directed to the pre-exposed stimulus, evidence supporting these mechanisms in humans is limited. The aim of this study is to determine if two variables, pre-exposure session spacing and multiple context pre-exposure, potentiate the hypothesized mechanisms of expected relevance and attention and, in turn, increase latent inhibition of dental fear. METHODS: In a virtual reality simulation, child and adult community members (ages 6 to 35) will take part in pre-exposure and conditioning trials, followed by short- and long-term tests of learning. A 100ms puff of 60 psi air to a maxillary anterior tooth will serve as the unconditioned stimulus. Pre-exposure session spacing (no spacing vs. sessions spaced) and multiple context pre-exposure (single context vs. multiple contexts) will be between-subject factors. Stimulus type (pre-exposed to-be conditioned stimulus, a non-pre-exposed conditioned stimulus, and an unpaired control stimulus) and trial will serve as within-subject factors. Baseline pain sensitivity will also be measured as a potential moderator. DISCUSSION: It is hypothesized that spaced pre-exposure and pre-exposure in multiple contexts will increase the engagement of the mechanisms of expected relevance and attention and increase the latent inhibition of dental fear. It is expected that the findings will add to theory on fear learning and provide information to aid the design of future interventions that leverage latent inhibition to reduce dental phobia.

A study protocol testing pre-exposure dose and compound pre-exposure on the mechanisms of latent inhibition of dental fear.

BACKGROUND: Dental stimuli can evoke fear after being paired - or conditioned - with aversive outcomes (e.g., pain). Pre-exposing the stimuli before conditioning can impair dental fear learning via a phenomenon known as latent inhibition. Theory suggests changes in expected relevance and attention are two mechanisms responsible for latent inhibition. In the proposed research, we test whether pre-exposure dose and degree of pre-exposure novelty potentiate changes in expected relevance and attention to a pre-exposed stimulus. We also assess if the manipulations alter latent inhibition and explore the possible moderating role of individual differences in pain sensitivity. METHODS: Participants will be healthy individuals across a wide range of ages (6 to 35 years), from two study sites. Participants will undergo pre-exposure and conditioning followed by both a short-term and long-term test of learning, all in a novel virtual reality environment. The unconditioned stimulus will be a brief pressurized puff of air to a maxillary anterior tooth. Pre-exposure dose (low vs. high) and pre-exposure novelty (element stimulus vs. compound stimuli) will be between-subject factors, with stimulus type (pre-exposed to-be conditioned stimulus, a non-pre-exposed conditioned stimulus, and an unpaired control stimulus) and trial as within-subject factors. Pain sensitivity will be measured through self-report and a cold pressor test. It is hypothesized that a larger dose of pre-exposure and compound pre-exposure will potentiate the engagement of the target mechanisms and thereby result in greater latent inhibition in the form of reduced fear learning. Further, it is hypothesized that larger effects will be observed in participants with greater baseline pain sensitivity. DISCUSSION: The proposed study will test whether pre-exposure dose and compound stimulus presentation change expected relevance and attention to the pre-exposed stimulus, and thereby enhance latent inhibition of dental fear. If found, the results will add to our theoretical understanding of the latent inhibition of dental fear and inform future interventions for dental phobia prevention.

The desire for side-effect information in pain treatment: an experimental analysis of contextual and individual difference factors.

ABSTRACT: Informing patients about potential side effects of pain treatment is a requirement that protects patients and aids decision making, but it increases the likelihood of unwanted nocebo side effects. If patients do not desire all side-effect information, it may be possible to ethically reduce nocebo effects through authorized concealment of side effects, whereby patients and clinicians engage in shared decision-making to regulate the disclosure of side-effect information. Currently, there is no experimental data clarifying the factors that causally influence desire for side-effect information in pain treatment. In 2 cross-sectional, between-subjects scenario experiments (experiment 1 N = 498, experiment 2 N = 501), 18 to 79-year-old community adults learned about a lower back pain treatment, and potential side-effect severity, frequency, and duration were manipulated. Individual differences in information avoidance were also recorded. In both experiments, participants reported high desire for side-effect information, but the desire was reduced when side effects were described as less severe, less frequent, and participants scored high in information avoidance. Results were not moderated by participants' level of contact with the health care system, chronic health condition, or clinical pain history. Additional analyses indicated that low side-effect severity and frequency lessen desire for side-effect information because these variables reduce belief that side-effect information will be needed in the future and lower feelings of anticipated regret. The experiments identify situational and individual-difference factors that decrease the desire for side-effect information and provide evidence on when and for whom it may be useful for physicians to engage in shared medical decision-making with the goal of reducing nocebo side effects.

The Use of Authorized Concealment to Minimize Nocebo Side Effects: A Survey of US Public Attitudes.

INTRODUCTION: To minimize nocebo effects, it may be possible to employ authorized concealment, in which clinicians tell patients about the nocebo phenomenon and ask if they would prefer not to be informed about mild treatment side effects. OBJECTIVE: The objective of the study was to understand public evaluations of authorized concealment for reducing nocebo effects. METHODS: An online cross-sectional survey was completed by a demographically diverse US national community sample between June 2 and 6, 2023. Participants were 1,012 adults residing in 48 states, ages ranging from 18 to 94 (mean = 43.2), 65.4% regularly taking medication, and 66.6% reporting a chronic physical or mental health condition. After learning about nocebo effects, participants rated and estimated their likelihood of consenting to four potential methods for authorized concealment of mild side effects. The four methods were ranked for preference and ranked again with the options of (1) receiving all side-effect information and (2) having the opportunity to select among disclosure methods. RESULTS: A majority of participants (86.2%) positively endorsed at least one authorized concealment method and 88.2% estimated they would consent to at least one method. Authorized concealment in which individuals learned only the most common side effects or had side-effect information available online received more positive ratings and rankings. A final ranking yielded preferences for receiving all side-effect information (30.4%) and having the opportunity to select side-effect disclosure method (31.8%). CONCLUSIONS: Our study suggests that many in the public could be open to authorized concealment for mild side effects when it is explained in reference to nocebo effects.

Suggestion Timing Moderates the Effects of Prior Pain Experiences on Pain Perception.

Two common elements in patient care are reoccurring painful events (eg, blood draws) and verbal suggestions from others for lessened pain. Research shows that verbal suggestions for lower pain can decrease subsequent pain perception from novel noxious stimuli, but it is less clear how these suggestions and prior painful experiences combine to influence the perception of a reoccurring painful event. The presented experiment tested the hypothesis that the order of these 2 factors influence pain perception for a reoccurring painful event. All participants (702 healthy college-student volunteers, 58% women, 85.5% White) experienced a novel painful event on one arm, then again on their other arm (now a familiar pain event). Participants who received the suggestion that they can tolerate more pain on the second arm relative to the first from the outset, before the initial pain event, perceived relatively less pain during the repeated event as compared to participants who received the same suggestion after the first painful event or no-suggestion (control). Given many pain events within medical contexts are, or become, familiar to patients, further researching the timing at which patients receive verbal suggestions for lower pain can inform practices to optimize the therapeutic, pain-reducing potential of such suggestions. PERSPECTIVE: Providing suggestions that a familiar pain event (ie, the second of 2) will be less painful than a prior event can reduce perceived pain for the familiar event depending on when it is presented. These findings can inform practices to optimize the therapeutic potential of verbal suggestions for reduced pain.

Study protocol of an investigation of attention and prediction error as mechanisms of action for latent inhibition of dental fear in humans.

BACKGROUND: Evidence suggests that dental anxiety and phobia are frequently the result of direct associative fear conditioning but that pre-exposure to dental stimuli prior to conditioning results in latent inhibition of fear learning. The mechanisms underlying the pre-exposure effect in humans, however, are poorly understood. Moreover, pain sensitivity has been linked to dental fear conditioning in correlational investigations and theory suggests it may moderate the latent inhibition effect, but this hypothesis has not been directly tested. These gaps in our understanding are a barrier to the development of evidence-based dental phobia prevention efforts. METHODS: Healthy volunteers between the ages of 6 and 35 years will be enrolled across two sites. Participants will complete a conditioning task in a novel virtual reality environment, allowing for control over pre-exposure and the examination of behaviour. A dental startle (a brief, pressurized puff of air to a tooth) will serve as the unconditioned stimulus. Using a within-subjects experimental design, participants will experience a pre-exposed to-be conditioned stimulus, a non-pre-exposed to-be conditioned stimulus, and a neutral control stimulus. Two hypothesized mechanisms, changes in prediction errors and attention, are expected to mediate the association between stimulus condition and fear acquisition, recall, and retention. To ascertain the involvement of pain sensitivity, this construct will be measured through self-report and the cold pressor task. DISCUSSION: Dental phobia negatively affects the dental health and overall health of individuals. This study aims to determine the mechanisms through which pre-exposure retards conditioned dental fear acquisition, recall, and retention. A randomized control trial will be used to identify these mechanisms so that they can be precisely targeted and maximally engaged in preventative efforts.

Social communication pathways to COVID-19 vaccine side-effect expectations and experience.

OBJECTIVE: Negative beliefs about medication and vaccine side-effects can spread rapidly through social communication. This has been recently documented with the potential side-effects from the COVID-19 vaccines. We tested if pre-vaccination social communications about side-effects from personal acquaintances, news reports, and social media predict post-vaccination side-effect experiences. Further, as previous research suggests that side-effects can be exacerbated by negative expectations, we assessed if personal expectations mediate the relationships between social communication and side-effect experience. METHOD: In a prospective longitudinal survey (N = 551), COVID-19 vaccine side-effect information from three sources-social media posts, news reports, and first-hand accounts from personal acquaintances-as well as side-effect expectations, were self-reported pre-vaccination. Vaccination side-effect experience was assessed post-vaccination. RESULTS: In multivariate regression analyses, the number of pre-vaccination social media post views (ß = 0.17) and impressions of severity conveyed from personal acquaintances (ß = 0.42) significantly predicted an increase in pre-vaccination side-effect expectations, and the same variables (ßs = 0.11, 0.14, respectively) predicted post-vaccination side-effect experiences. Moreover, pre-vaccination side-effect expectations mediated the relationship between both sources of social communication and experienced side-effects from a COVID-19 vaccination. CONCLUSIONS: This study identifies links between personal acquaintance and social media communications and vaccine side-effect experiences and provides evidence that pre-vaccination expectations account for these relationships. The results suggest that modifying side-effect expectations through these channels may change the side-effects following a COVID-19 vaccination as well as other publicly discussed vaccinations and medications.

Choice and the nocebo effect: If a little is good, more is better?

OBJECTIVE: Lack of choice over treatment may increase the nocebo effect, whereby unpleasant side effects can be triggered by the treatment context, beyond any inherent physiological effects of the treatment itself. Excessive choice may also increase the nocebo effect. The current studies tested these possibilities. METHOD: Participants took part in studies ostensibly investigating the influence of beta-blockers (Study 1, n = 71) and benzodiazepines (Study 2, n = 120) on anxiety. All treatments were placebos. In Study 1, participants were randomly allocated to three groups: no-treatment control, no-choice, and choice between two treatments. In Study 2, a ten-choice group was added. Participants were warned about possible treatment side effects. These warned symptoms were assessed, and scores summed. Nocebo effects were evidenced by significantly higher warned symptoms scores in any placebo-treated group compared to the control group. RESULTS: In both studies, the no-choice groups experienced a nocebo effect (S1: p = .003, ηp2= 0.121; S2: p = .022, ηp2= 0.045). A significant nocebo effect was not present in groups who chose between two treatments (S1: p = .424, ηp2= 0.009; S2: p = .49, ηp2= 0.004). In Study 2, choosing between ten treatments resulted in a nocebo effect (p = .006, ηp2= 0.065). CONCLUSION: Lack of choice resulted in the development of nocebo effects, while having a limited choice between two placebos did not generate significant nocebo effects. However, a larger choice between ten placebos generated a nocebo effect of similar magnitude to lack of choice. Facilitating (some) choice in medical care may reduce the development of nocebo effects, but more extensive choice options may not offer similar benefits.

Development of a Measure of Fearful Implicit Associations with Dental Stimuli in Youth.

Youth with dental anxiety are at an increased risk of poor oral health but current tools used to identify dental anxiety in children in clinical settings are hampered by several limitations. This study assessed the psychometric properties of a measure of implicit associations with dental stimuli, the Affective Misattribution Procedure for dental stimuli (AMP-D) in 68 youth between the ages of 9 and 17 years. Measures of self-reported dental anxiety and parental perceptions of child dental anxiety were also administered. The internal consistency of the AMP-D was high (KR-20 = 0.96) and 1-week test-retest reliability was in the acceptable range (r = 0.75). The AMP-D was correlated with self-reported dental anxiety, providing evidence of construct validity. The psychometric properties of the AMP-D suggest it could be a useful tool in identifying youth with dental anxiety, particularly when concerns regarding self-representation may compromise the validity of self-reported anxiety.

Development and cross-national investigation of a model explaining participation in WHO-recommended and placebo behaviours to prevent COVID-19 infection.

To protect themselves from COVID-19, people follow the recommendations of the authorities, but they also resort to placebos. To stop the virus, it is important to understand the factors underlying both types of preventive behaviour. This study examined whether our model (developed based on the Health Belief Model and the Transactional Model of Stress) can explain participation in WHO-recommended and placebo actions during the pandemic. Model was tested on a sample of 3346 participants from Italy, Japan, Poland, Korea, Sweden, and the US. It was broadly supported: objective risk and cues to action showed both direct and indirect (through perceived threat) associations with preventive behaviours. Moreover, locus of control, decision balance, health anxiety and preventive coping moderated these relationships. Numerous differences were also found between countries. We conclude that beliefs about control over health and perceived benefits of actions are critical to the development of interventions to improve adherence to recommendations.

Do Side Effects to the Primary COVID-19 Vaccine Reduce Intentions for a COVID-19 Vaccine Booster?

BACKGROUND: Vaccines are being administered worldwide to combat the COVID-19 pandemic. Vaccine boosters are essential for maintaining immunity and protecting against virus variants. The side effects of the primary COVID-19 vaccine (e.g., headache, nausea), however, could reduce intentions to repeat the vaccination experience, thereby hindering global inoculation efforts. PURPOSE: The aim of this research was to test whether side effects of a primary COVID-19 vaccine relate to reduced intentions to receive a COVID-19 booster. The secondary aim was to test whether psychological and demographic factors predict booster intentions. METHODS: Secondary data analyses were conducted on a U.S. national sample of 551 individuals recruited through the online platform Prolific. Key measures in the dataset were side effects reported from a primary COVID-19 vaccination and subsequent intentions to receive a booster vaccine. Psychological and demographic variables that predicted primary vaccination intentions in prior studies were also measured. RESULTS: Booster intentions were high. COVID-19 booster vaccine intentions were uncorrelated with the number of side effects, intensity of side effects, or occurrence of an intense side effect from the primary COVID-19 vaccine. Correlational and regression analyses indicated intentions for a booster vaccination increased with positive vaccination attitudes, trust in vaccine development, worry about the COVID-19 pandemic, low concern over vaccine side effects, and democratic political party affiliation. CONCLUSIONS: Side effects of a primary COVID-19 vaccine were not directly associated with lower intentions to receive a booster of the COVID-19 vaccine early in the pandemic. However, many variables that predict primary vaccination intentions also predict booster intentions.

The influence of message framing on nocebo headaches: Findings from a randomized laboratory design.

Attribute framing presents an ethically sound approach for reducing adverse nocebo effects. In past studies, however, attribute framing has not always decreased nocebo effects. The present study used a sham tDCS procedure to induce nocebo headaches to explore factors that may contribute to the efficacy of attribute framing. Participants (N = 174) were randomized to one of three between-subject conditions: a no-headache instruction (control) condition and two conditions in which headaches were described as either 70% likely (negative framing) to occur or 30% unlikely (positive framing) to occur. Results revealed nocebo headaches in both framing conditions, as compared to the control condition. Attribute framing did not influence headache measures recorded during the sham tDCS task, but framing did have a modest influence on one of two headache items completed after the task. Results suggest that attribute framing could have a stronger influence on delayed nocebo effect measures or retrospective symptom reports; a finding that may explain inconsistencies in the existing framing-nocebo effect literature. Exploratory analyses also revealed that low negative affect was associated with stronger nocebo and attribute framing effects, although these effects were found on only a few headache measures. It is concluded that researchers should further investigate the influence of attribute framing on nocebo headaches as a function of both timing and emotional factors.

Choice and the Placebo Effect: A Meta-analysis.

BACKGROUND: Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect. PURPOSE: To estimate the effect size of choice on the placebo effect and identify any moderators of this effect. METHODS: Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice. RESULTS: Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges' g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice. CONCLUSIONS: Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.

Handwashing Message Type Predicts Behavioral Intentions in the United States at the Beginning of the Global COVID-19 Pandemic.

Handwashing has been widely recommended to reduce the spread of COVID-19. Despite this, handwashing behavior remains low in the general public. Social marketing has been employed as a successful health promotion strategy for changing many health behaviors in the past. The present study examines if message framing influences the effectiveness of a handwashing health promotion messages at the early stages of the COVID-19 pandemic. In a between-subjects cross-sectional experiment, participants (N = 344) in the United States were randomly assigned to view one of four handwashing messages or a control message before completing self-report measures of attitudes, emotions, readiness to change, and behavioral intentions around handwashing. Simple handwashing messages were presented with different framings, including a simple exchange message, a gain message, a social norm appeal, and a guilt appeal. Results revealed that message type influenced handwashing behavioral intentions and emotions. Post-hoc comparisons revealed that the simple exchange message produced significantly higher intentions than other messages and that only the simple exchange message significantly differed from the control message on emotions regarding handwashing. Mediational analyses showed handwashing emotions fully mediated the relationship between messaging and handwashing intentions. This mediation effect was moderated by age, such that it occurred for the younger and middle age participants, but not older participants. These results suggest that even simple, brief, and easily conveyable messages can positively impact behavioral intentions around handwashing during the early stages of a health crisis. Consistent with recent research comparing affective and cognitive pathways for health behavior, the mediational analysis suggests that effect of the simple exchange message on intentions was due to increased positive emotions around handwashing.

Using Positive Attribute Framing to Attenuate Nocebo Side Effects: A Cybersickness Study.

BACKGROUND: Side effect warnings can contribute directly to their occurrence via the nocebo effect. This creates a challenge for clinicians and researchers, because warnings are necessary for informed consent, but can cause harm. Positive framing has been proposed as a method for reducing nocebo side effects whilst maintaining the principles of informed consent, but the limited available empirical data are mixed. PURPOSE: To test whether positive attribute framing reduces nocebo side effects relative to negative framing, general warning, and no warning. METHODS: Ninety-nine healthy volunteers were recruited under the guise of a study on virtual reality (VR) and spatial awareness. Participants were randomized to receive positively framed ("7 out of 10 people will not experience nausea"), negatively framed ("3 out of 10 people will experience nausea"), general ("a proportion of people will experience nausea"), or no side effect warnings prior to VR exposure. RESULTS: Receiving a side effect warning increased VR cybersickness relative to no warning overall, confirming that warnings can induce nocebo side effects. Importantly, however, positive framing reduced cybersickness relative to both negative framing and the general warning, with no difference between the latter two. Further, there was no difference in side effects between positive framing and no warning. CONCLUSIONS: These findings suggest that positive framing not only reduces nocebo side effects relative to negative framing and general warnings, but actually prevents nocebo side effects from occurring at all. As such, positive attribute framing may be a cheap and ethical way to reduce nocebo side effects.

Underpredicting pain: an experimental investigation into the benefits and risks.

ABSTRACT: Expectancies can shape pain and other experiences. Generally, experiences change in the direction of what is expected (ie, assimilation effects), as seen with placebo effects. However, in case of large expectation-experience discrepancies, experiences might change away from what is expected (ie, contrast effects). Previous research has demonstrated contrast effects on various outcomes, but not pain. We investigated the effects of strong underpredictions of pain on experienced pain intensity. In addition, we assessed related outcomes including (certainty of) expectations, fear of pain, pain unpleasantness, autonomic responses, and trust. Healthy participants (study 1: n = 81 and study 2: n = 123) received verbal suggestions that subsequent heat stimuli would be moderately or highly painful (correct prediction), mildly painful (medium underprediction; study 2 only), or nonpainful (strong underprediction). Both studies showed that participants experienced less intense pain upon strong underprediction than upon correct prediction (ie, assimilation). Expected pain, fear of pain, and pain unpleasantness were generally also lowered. However, strong underprediction simultaneously lowered certainty of expectations and trust in the experimenter. Study 2 indicated that the effects of strong underprediction vs medium underprediction generally did not differ. Moreover, study 2 provided some indications for reduced heart rate and skin conductance levels but increased skin conductance responses upon strong underprediction. In conclusion, even strong underpredictions of pain can reduce pain (ie, cause assimilation), although not significantly more than medium underpredictions. However, strong underpredictions can cause uncertainty and undermine trust. These findings suggest that healthcare providers may wish to be cautious with providing overly positive information about painful medical procedures.

What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus.

INTRODUCTION: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. OBJECTIVE: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. METHODS: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. RESULTS: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. CONCLUSIONS: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients' needs, and on developing standardized disclosure training modules for clinicians.