What is associated with painful polyneuropathy? A cross-sectional analysis of symptoms and signs in patients with painful and painless polyneuropathy.

ABSTRACT: It is still unclear how and why some patients develop painful and others painless polyneuropathy. The aim of this study was to identify multiple factors associated with painful polyneuropathies (NeuP). A total of 1181 patients of the multicenter DOLORISK database with painful (probable or definite NeuP) or painless (unlikely NeuP) probable or confirmed neuropathy were investigated clinically, with questionnaires and quantitative sensory testing. Multivariate logistic regression including all variables (demographics, medical history, psychological symptoms, personality items, pain-related worrying, life-style factors, as well as results from clinical examination and quantitative sensory testing) and machine learning was used for the identification of predictors and final risk prediction of painful neuropathy. Multivariate logistic regression demonstrated that severity and idiopathic etiology of neuropathy, presence of chronic pain in family, Patient-Reported Outcomes Measurement Information System Fatigue and Depression T-Score, as well as Pain Catastrophizing Scale total score are the most important features associated with the presence of pain in neuropathy. Machine learning (random forest) identified the same variables. Multivariate logistic regression archived an accuracy above 78%, random forest of 76%; thus, almost 4 out of 5 subjects can be classified correctly. This multicenter analysis shows that pain-related worrying, emotional well-being, and clinical phenotype are factors associated with painful (vs painless) neuropathy. Results may help in the future to identify patients at risk of developing painful neuropathy and identify consequences of pain in longitudinal studies.

Attentional Processes in Pain: The Importance of Context and Attentional Alignment.

The attentional bias literature has consistently failed to take context into account. We developed a novel paradigm in immersive virtual reality (VR) with pain stimuli where it would be adaptive or nonadaptive to attend to the stimuli. Participants had to indicate the location of the stimuli. Seventy participants were recruited. The VR-attention task assessed overall attentional bias (the tendency to prioritize pain compared with nonpain stimuli) and attentional alignment (the tendency to attend to pain more in adaptive than nonadaptive situations). Pain tolerance and threshold were measured using electrocutaneous stimulation and thermal pain. We conducted 2 (context: adaptive vs nonadaptive) × 2 (congruence: congruent vs incongruent) Analysis of Covariance, controlling for threat. Participants responded to pain probes more quickly in adaptive than nonadaptive contexts. There was an overall bias away from pain-related stimuli (avoidance) in reaction time to the target. There was also an interaction where avoidance was greater in nonadaptive contexts, indicative of attentional alignment. For gaze behavior, both attentional alignment and attentional bias were observed for latency to first fixation on the target, such that participants showed vigilance for pain particularly in the adaptive context. Attentional alignment was correlated with threshold and tolerance from electrocutaneous stimulation but not thermal pain. In conclusion, we found overall attentional biases indicating vigilance (latency to first fixation) and avoidance (response to target). We also found that participants evidenced a pattern of attention favoring adaptive over nonadaptive contexts (attentional alignment). It was attentional alignment, but not overall attentional bias, that predicted pain tolerance and threshold. PERSPECTIVE: The study explored attentional processes in pain through a novel paradigm designed in VR. The results found that positive attentional alignment, or the tendency to attend to pain more in adaptive contexts rather than nonadaptive contexts, predicted pain outcomes.

Beyond the modified dot-probe task: A meta-analysis of the efficacy of alternate attention bias modification tasks across domains.

Attention biases towards disease-relevant cues have been implicated in numerous disorders and health conditions, such as anxiety, cancer, drug-use disorders, and chronic pain. Attention bias modification (ABM) has shown that changing attention biases can change related emotional processes. ABM most commonly uses a modified dot-probe task, which has received increasing criticism regarding its reliability and inconsistent findings. The purpose of the present review was thus to systematically review and meta-analyse alternative tasks used in ABM research. We sought to examine whether alternative tasks significantly changed attention biases and emotional outcomes, and critically examined whether relevant sample, task and intervention characteristics moderated each of these effect sizes. Seventy-four (completer n = 15,294) study level comparisons were included in the meta-analysis. Overall, alternative ABM designs had a medium effect on changing biases (g = 0.488), and a small, but significant effect on improving clinical outcomes (g = 0.117). We found this effect to be significantly larger for studies which successfully changed biases compared to those that did not. Across all tasks, it appeared that targeting engagement biases results in the largest change to attention biases. Importantly, we found tasks incorporating gaze-contingency - encouraging engagement with non-biased stimuli - show the most promise for improving emotional outcomes.

Identifying app components that promote physical activity: a group concept mapping study.

Background: Digital interventions are a promising avenue to promote physical activity in healthy adults. Current practices recommend to include end-users early on in the development process. This study focuses on the wishes and needs of users regarding an a mobile health (mHealth) application that promotes physical activity in healthy adults, and on the differences between participants who do or do not meet the World Health Organization's recommendation of an equivalent of 150 minutes of moderate intensity physical activity. Methods: We used a mixed-method design called Group Concept Mapping. In a first phase, we collected statements completing the prompt "In an app that helps me move more, I would like to see/ do/ learn the following…" during four brainstorming sessions with physically inactive individuals (n = 19). The resulting 90 statements were then sorted and rated by a new group of participants (n = 46). Sorting data was aggregated, and (dis)similarity matrices were created using multidimensional scaling. Hierarchical clustering was applied using Ward's method. Analyses were carried out for the entire group, a subgroup of active participants and a subgroup of inactive participants. Explorative analyses further investigated ratings of the clusters as a function of activity level, gender, age and education. Results: Six clusters of statements were identified, namely 'Ease-of-use and Self-monitoring', 'Technical Aspects and Advertisement', 'Personalised Information and Support', 'Motivational Aspects', 'Goal setting, goal review and rewards', and 'Social Features'. The cluster 'Ease-of-use and Self-monitoring' was rated highest in the overall group and the active subgroup, whereas the cluster 'Technical Aspects and Advertisement' was scored as most relevant in the inactive subgroup. For all groups, the cluster 'Social Features' was scored the lowest. Explorative analysis revealed minor between-group differences. Discussion: The present study identified priorities of users for an mHealth application that promotes physical activity. First, the application should be user-friendly and accessible. Second, the application should provide personalized support and information. Third, users should be able to monitor their behaviour and compare their current activity to their past performance. Fourth, users should be provided autonomy within the app, such as over which and how many notifications they would like to receive, and whether or not they want to engage with social features. These priorities can serve as guiding principles for developing mHealth applications to promote physical activity in the general population.

Investigating experiences of people with advanced breast or lung cancer in their natural context: protocol for an experience sampling study.

INTRODUCTION: People with advanced cancer can experience a wide range of multidimensional symptoms or concerns, but little is known about when and how these fluctuate in daily life. Experience sampling methods (ESMs) involve repeated self-reports in people's natural contexts aimed at uncovering everyday life experiences. ESM has limited recall bias and good ecological validity but might be burdensome to patients. This study aims to pretest and evaluate the feasibility and clinical utility of a validated ESM and use it to explore everyday experiences of people living with advanced breast or lung cancer. METHODS AND ANALYSIS: In step 1, we will optimise our ESM method by pretesting it through usability interviews and a pilot ESM study. In step 2, we will evaluate and use the ESM method through an observational ESM study to investigate the daily experiences of people with advanced breast or lung cancer. Step 2 also includes interviews with healthcare professionals to determine the clinical utility of ESM in oncology. Participants will complete a digital questionnaire ten times per day, measuring momentary experiences in the physical, psychological, social, spiritual-existential domains and context. Multilevel regression models will analyse fluctuations and temporal relations among measured experiences and context. Analyses also include evaluation of compliance and participation rates. We will apply content analysis to the usability interviews and follow-up interviews of the pilot ESM study. ETHICS AND DISSEMINATION: We obtained approval from the ethics committees of the University Hospitals of Brussels (BUN: 1432023000043) and Ghent (ONZ-2023-0136). Results will be published in open-access, peer-reviewed journals and presented at conferences. If ESM appears feasible in this population, it could offer new insights into the daily experiences and help optimise support for people with advanced cancer.

Narrative bias ("spin") is common in randomised trials and systematic reviews of cannabinoids for pain.

ABSTRACT: We define narrative bias as a tendency to interpret information as part of a larger story or pattern, regardless of whether the facts support the full narrative. Narrative bias in title and abstract means that results reported in the title and abstract of an article are done so in a way that could distort their interpretation and mislead readers who had not read the whole article. Narrative bias is often referred to as "spin." It is prevalent in abstracts of scientific papers and is impactful because abstracts are often the only part of an article read. We found no extant narrative bias instrument suitable for exploring both efficacy and safety statements in randomized trials and systematic reviews of pain. We constructed a 6-point instrument with clear instructions and tested it on randomised trials and systematic reviews of cannabinoids and cannabis-based medicines for pain, with updated searches to April 2021. The instrument detected moderate or severe narrative bias in the title and abstract of 24% (8 of 34) of randomised controlled trials and 17% (11 of 64) of systematic reviews; narrative bias for efficacy and safety occurred equally. There was no significant or meaningful association between narrative bias and study characteristics in correlation or cluster analyses. Bias was always in favour of the experimental cannabinoid or cannabis-based medicine. Put simply, reading title and abstract only could give an incorrect impression of efficacy or safety in about 1 in 5 papers reporting on these products.

Synergizing the Behavior Change Wheel and a Cocreative Approach to Design a Physical Activity Intervention for Adolescents and Young Adults With Intellectual Disabilities: Development Study.

BACKGROUND: There is a need for physical activity promotion interventions in adolescents and young adults with intellectual disabilities. Current interventions have shown limited effectiveness, which may be attributed to the absence of theory and a population-specific development. Combining a planning model (including theory) and cocreation with the target audience during intervention development could potentially address this gap. OBJECTIVE: This study aimed to report the systematic development of the Move it, Move ID! intervention by describing how the 8 different steps of the Behavior Change Wheel (BCW) were applied and present the results that emerged from those steps. In doing so, the (theoretical) content of the intervention is described in detail. METHODS: A total of 23 adolescents and young adults (aged 14-22 years) with mild to moderate intellectual disabilities were designated as cocreators of the intervention. Across 2 groups, 6 similar cocreation sessions were organized in each. The content and sequence of the sessions were structured to align with the 8 steps of the BCW. All sessions were recorded and transcribed verbatim. Both a deductive (ie, steps of the BCW) and inductive (ie, resonating the voice of the participants) analysis approach were applied specifically focusing on identifying and describing the findings within each of the BCW steps. RESULTS: After behavioral analysis (steps 1-4), 10 intervention goals were chosen and linked to Capability, Opportunity, and Motivation-Behavior components (theory within the BCW) that needed to be addressed. Psychological capability, social opportunity, and reflective motivation were emphasized as the first targets to focus on. A key finding was the urge for real-life social connectedness and social integration, which makes the social component as part of physical activity a central theme to focus on within intervention development. Judgments on the most suitable intervention functions (step 5) and behavior change techniques (step 7) were explained. When discussing the mode of delivery of the intervention (step 8), it was underscored that solely relying on a mobile health app would not fulfill participants' social needs. Hence, the chosen intervention adopts a dyadic approach in which young individuals with intellectual disabilities are matched with peers without intellectual disabilities to engage in physical activities together, with a mobile app playing a supportive role in this partnership. CONCLUSIONS: The transparent description of the development process highlights why certain intervention components and behavior change techniques were chosen and how they are intertwined by means of the selected intervention design. This paper provides a detailed blueprint for practitioners wanting to integrate the BCW and its associated behavior change techniques, in combination with actively involving the target group, into their intervention development for people with intellectual disabilities.

A mobile healthy lifestyle intervention to promote mental health in adolescence: a mixed-methods evaluation.

BACKGROUND: A healthy lifestyle may improve mental health. It is yet not known whether and how a mobile intervention can be of help in achieving this in adolescents. This study investigated the effectiveness and perceived underlying mechanisms of the mobile health (mHealth) intervention #LIFEGOALS to promote healthy lifestyles and mental health. #LIFEGOALS is an evidence-based app with activity tracker, including self-regulation techniques, gamification elements, a support chatbot, and health narrative videos. METHODS: A quasi-randomized controlled trial (N = 279) with 12-week intervention period and process evaluation interviews (n = 13) took place during the COVID-19 pandemic. Adolescents (12-15y) from the general population were allocated at school-level to the intervention (n = 184) or to a no-intervention group (n = 95). Health-related quality of life (HRQoL), psychological well-being, mood, self-perception, peer support, resilience, depressed feelings, sleep quality and breakfast frequency were assessed via a web-based survey; physical activity, sedentary time, and sleep routine via Axivity accelerometers. Multilevel generalized linear models were fitted to investigate intervention effects and moderation by pandemic-related measures. Interviews were coded using thematic analysis. RESULTS: Non-usage attrition was high: 18% of the participants in the intervention group never used the app. An additional 30% stopped usage by the second week. Beneficial intervention effects were found for physical activity (χ21 = 4.36, P = .04), sedentary behavior (χ21 = 6.44, P = .01), sleep quality (χ21 = 6.11, P = .01), and mood (χ21 = 2.30, P = .02). However, effects on activity-related behavior were only present for adolescents having normal sports access, and effects on mood only for adolescents with full in-school education. HRQoL (χ22 = 14.72, P < .001), mood (χ21 = 6.03, P = .01), and peer support (χ21 = 13.69, P < .001) worsened in adolescents with pandemic-induced remote-education. Interviewees reported that the reward system, self-regulation guidance, and increased health awareness had contributed to their behavior change. They also pointed to the importance of social factors, quality of technology and autonomy for mHealth effectiveness. CONCLUSIONS: #LIFEGOALS showed mixed results on health behaviors and mental health. The findings highlight the role of contextual factors for mHealth promotion in adolescence, and provide suggestions to optimize support by a chatbot and narrative episodes. TRIAL REGISTRATION: ClinicalTrials.gov [NCT04719858], registered on 22/01/2021.

Reconceptualizing sensitization in pain: back to basics.

Fillingim RB. Redefining sensitization could be a sensitive issue. PAIN Rep 2024;9:e1126.

The relationship of affective and bodily states with goals and plans to increase physical activity: An 8-day study in students.

Planning is an important tool to translate intentions into physical activity (PA) behavior. Affective and bodily states are known to influence how much PA individuals perform, but their impact on to formulation of PA plans is not yet known. The aim of the current study is to explore the effect of within- and between-subject variations in affective and bodily states on the content of PA goals and plans. Over eight consecutive days, 362 students created action and coping plans to achieve their daily PA goals. They also reported their affective and bodily states. Generalized linear mixed effect models were used to analyze the associations between these states and the content of the goals and plans. The results showed that both between- and within-subject variations in affective and bodily states were associated with goals formulated in terms of minutes, the intensity and context of planned activities, and anticipated barriers, though more effects were found for within-subject differences. Affective and bodily states impact daily PA goals and plans, highlighting the dynamic nature of planning. Our findings can be a first step toward personalized suggestions for goals, action plans, and coping strategies that are based on individual affective and bodily states.

A synthesis of meta-analyses of mindfulness-based interventions in pain.

ABSTRACT: Mindfulness interventions have become popular in recent decades, with many trials, systematic reviews, and meta-analyses of the impact of mindfulness-based interventions (MBIs) on pain. Although many meta-analyses provide support for MBIs, the results are more mixed than they at first appear. The aim of this umbrella review was to determine the strength of evidence for MBIs by synthesizing available meta-analyses in pain. We conducted a systematic search in 5 databases and extracted data from published meta-analyses as the unit of analysis. For each outcome, we reported the range of effect sizes observed across studies and identified the largest meta-analysis as the "representative" study. We separately analysed effect sizes for different pain conditions, different types of MBIs, different control groups, and different outcomes. We identified 21 meta-analyses that included 127 unique studies. According to Assessment of Multiple Systematic Review ratings, the meta-analyses ranged from very strong to weak. Overall, there was an impact of MBIs on pain severity, anxiety, and depression but not pain interference or disability. When conditions were considered in isolation, only fibromyalgia and headache benefited significantly from MBIs. Mindfulness-based interventions were more efficacious for pain severity than passive control conditions but not active control conditions. Only pain severity and anxiety were affected by MBIs at follow-up. Overall, our results suggest that individual meta-analyses of MBIs may have overestimated the efficacy of MBIs in a range of conditions. Mindfulness-based interventions likely have a role in pain management but should not be considered a panacea.

Updated recommendations on measures for clinical trials in pediatric chronic pain: a multiphase approach from the Core Outcomes in Pediatric Persistent Pain (Core-OPPP) Workgroup.

ABSTRACT: Many gaps remain in finding effective, safe, and equitable treatments for children and adolescents with chronic pain and in accessing treatments in different settings. A major goal of the field is to improve assessment of pain and related experience. Valid and reliable patient-reported outcome measures are critical for advancing knowledge of clinical interventions for pediatric chronic pain. Building on the work of the Ped-IMMPACT group, we previously updated a core outcome set (COS) for pediatric chronic pain clinical trials using stakeholder feedback from providers, youth, and parents. The new COS includes 3 mandatory domains: pain severity, pain-related interference with daily living, and adverse events and 4 optional domains: overall well-being, emotional functioning, physical functioning, and sleep quality. The aim of this study was to use a multiphased approach to recommend specific measures for each of the 7 domains identified in our new COS for pediatric chronic pain. We synthesized evidence through conducting the following: (1) a Delphi study of experts to identify candidate measures for the new COS domains, (2) a review phase to gather evidence for measurement properties for candidate measures, and (3) an expert consensus conference to reach agreement on measurement recommendations. Final recommendations included 9 patient-reported measures. Important contextual considerations are discussed, and guidance is provided regarding strengths and limitations of the recommendations. Implementation of these recommendations may be enhanced by widespread dissemination and ease of access to measurement tools.

Building on Existing Classifications of Behavior Change Techniques to Classify Planned Coping Strategies: Physical Activity Diary Study.

BACKGROUND: When trying to be more physically active, preparing for possible barriers by considering potential coping strategies increases the likelihood of plan enactment. Digital interventions can support this process by providing personalized recommendations for coping strategies, but this requires that possible coping strategies are identified and classified. Existing classification systems of behavior change, such as the compendium of self-enactable techniques, may be reused to classify coping strategies in the context of physical activity (PA) coping planning. OBJECTIVE: This study investigated whether coping strategies created by a student population to overcome barriers to be physically active can be mapped onto the compendium of self-enactable techniques and which adaptations or additions to the frameworks are needed. METHODS: In total, 359 Flemish university students created action and coping plans for PA for 8 consecutive days in 2020, resulting in 5252 coping plans. A codebook was developed iteratively using the compendium of self-enactable techniques as a starting point to code coping strategies. Additional codes were added to the codebook iteratively. Interrater reliability was calculated, and descriptive statistics were provided for the coping strategies. RESULTS: Interrater reliability was moderate (Cohen κ=0.72) for the coded coping strategies. Existing self-enactable techniques covered 64.6% (3393/5252) of the coded coping strategies, and added coping strategies covered 28.52% (n=1498). The remaining coping strategies could not be coded as entries were too vague or contained no coping strategy. The added classes covered multiple ways of adapting the original action plan, managing one's time, ensuring the availability of required material, and doing the activity with someone else. When exploring the data further, we found that almost half (n=2371, 45.1%) of the coping strategies coded focused on contextual factors. CONCLUSIONS: The study's objective was to categorize PA coping strategies. The compendium of self-enactable techniques addressed almost two-thirds (3393/5252, 64.6%) of these strategies, serving as valuable starting points for classification. In total, 9 additional strategies were integrated into the self-enactable techniques, which are largely absent in other existing classification systems. These new techniques can be seen as further refinements of "problem-solving" or "coping planning." Due to data constraints stemming from the COVID-19 pandemic and the study's focus on a healthy Flemish student population, it is anticipated that more coping strategies would apply under normal conditions, in the general population, and among clinical groups. Future research should expand to diverse populations and establish connections between coping strategies and PA barriers, with ontologies recommended for this purpose. This study is a first step in classifying the content of coping strategies for PA. We believe this is an important and necessary step toward digital health interventions that incorporate personalized suggestions for PA coping plans.

The effect of psychological factors on pain outcomes: lessons learned for the next generation of research.

Big data and machine learning techniques offer opportunities to investigate the effects of psychological factors on pain outcomes. Nevertheless, these advances can only deliver when the quality of the data is high and the underpinning causal assumptions are considered. We argue that there is room for improvement and identify some challenges in the evidence base concerning the effect of psychological factors on the development and maintenance of chronic pain. As a starting point, 3 basic tenets of causality are taken: (1) cause and effect differ from each other, (2) the cause precedes the effect within reasonable time, and (3) alternative explanations are ruled out. Building on these tenets, potential problems and some lessons learned are provided that the next generation of research should take into account. In particular, there is a need to be more explicit and transparent about causal assumptions in research. This will lead to better research designs, more appropriate statistical analyses, and constructive discussions and productive tensions that improve our science.

Within-Person Associations of Accelerometer-Assessed Physical Activity With Time-Varying Determinants in Older Adults: Time-Based Ecological Momentary Assessment Study.

BACKGROUND: Despite the availability of physical activity (PA) interventions, many older adults are still not active enough. This might be partially explained by the often-limited effects of PA interventions. In general, health behavior change interventions often do not focus on contextual and time-varying determinants, which may limit their effectiveness. However, before the dynamic tailoring of interventions can be developed, one should know which time-dependent determinants are associated with PA and how strong these associations are. OBJECTIVE: The aim of this study was to examine within-person associations between multiple determinants of the capability, opportunity, motivation, and behavior framework assessed using Ecological Momentary Assessment (EMA) and accelerometer-assessed light PA, moderate to vigorous PA, and total PA performed at 15, 30, 60, and 120 minutes after the EMA trigger. METHODS: Observational data were collected from 64 healthy older adults (36/64, 56% men; mean age 72.1, SD 5.6 y). Participants were asked to answer a time-based EMA questionnaire 6 times per day that assessed emotions (ie, relaxation, satisfaction, irritation, and feeling down), the physical complaint fatigue, intention, intention, and self-efficacy. An Axivity AX3 was wrist worn to capture the participants' PA. Multilevel regression analyses in R were performed to examine these within-person associations. RESULTS: Irritation, feeling down, intention, and self-efficacy were positively associated with subsequent light PA or moderate to vigorous PA at 15, 30, 60, or 120 minutes after the trigger, whereas relaxation, satisfaction, and fatigue were negatively associated. CONCLUSIONS: Multiple associations were observed in this study. This knowledge in combination with the time dependency of the determinants is valuable information for future interventions so that suggestions to be active can be provided when the older adult is most receptive.

Subliminal attentional bias modification training for itch.

Introduction: Itch is unpleasant and induces the urge to scratch. This is adaptive to remove the itch-inducing stimulus from the skin. Accordingly, itch draws attention to protect our bodily integrity. Recent studies investigated whether attention is preferentially drawn towards its location, i.e., attentional bias (AB), and also whether this bias could be changed in healthy individuals. So far, results are mixed concerning the existance of an attentional bias towards itch stimuli in healthy individuals as well as the impact of modifications. However, available studies have typically focused on conscious processing and might miss preconscious aspects of attention and potential biases at these stages. Methods: This study included 117 healthy individuals who underwent a subliminal Attentional Bias Modification (ABM)- training for itch based on a dot-probe paradigm with itch- related pictures. Participants were randomly assigned to a training towards itch group, a training away from itch group and a control group. This was done by manipulating the itch-target congruency of the dot-probe task during a training block. Pre- and post-training assessments were regular dot-probe tasks. Exploratorily, also attentional inhibition, cognitive flexibility and itch-related cognitions were assessed. Lastly, participants received an itchy stimulus on the inner forearm before and after the ABM-training to assess potential effects on itch sensitivity. Results: Results showed no AB towards itch across groups at baseline, i.e., pre-training, but an AB away from itch, hence, avoidance of itch, post-training. Further analyses showed that this effect was driven by an attentional bias away from itch in the control group, while there were no significant effects in the experimental groups. There was no effect on itch sensitivity. Conclusion: These findings are in line with recent studies on conscious ABM-training for itch and pain that also did not find significant training effects. Therefore, it is suggested that the field of AB might need to reconsider the current assessment of AB. Moreover, AB is probably a dynamic process that is highly dependent on current itch-related goals and relevance of itch in a specific situation. This suggests that processes probably differ in patients with chronic itch and that also ABM-training might work differently in these populations. Clinical trial registration: https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7561, identifier NTR7561.

In search of conditioned pain: an experimental analysis.

ABSTRACT: There is an ongoing debate about whether pain can be classically conditioned, but surprisingly, evidence is scarce. Here, we report 3 experiments investigating this idea. In a virtual reality task, healthy participants were approached and touched near or on their hand with a coloured pen (blue or yellow). During acquisition, participants learned that one of the colours of the pen (CS+) was predictive of a painful electrocutaneous stimulus (ECS) whereas the other coloured pen (CS-) was not. During the test phase, more frequent reports of experiencing an US when none was delivered ("false alarm") for the CS+ vs CS- qualified as evidence of conditioned pain. Notable differences between experiments were that the US was delivered when the pen touched a spot between the thumb and index finger (experiment 1; n = 23), when it virtually touched the hand (experiment 2; n = 28) and when participants were informed that the pen caused pain rather than simply predicting something (experiment 3; n = 21). The conditioning procedure proved successful in all 3 experiments: Self-reported fear, attention, pain, fear, and US expectancy were higher ( P < 0.0005) for the CS+ than the CS-. There was no evidence for conditioned pain in experiment 1, but there was some evidence in experiments 2 and 3. Our findings indicate that conditioned pain may exist, albeit most likely in rare cases or under specific situations. More research is needed to understand the specific conditions under which conditioned pain exists and the underlying processes (eg, response bias).