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Depression and anxiety co-occur with chronic pain, and all three are thought to be caused by dysregulation of shared brain systems related to emotional processing associated with body sensations. Understanding the connection between emotional states, pain, and bodily sensations may help understand chronic pain conditions. We developed a mobile platform for measuring pain, emotions, and associated bodily feelings in chronic pain patients in their daily life conditions. Sixty-five chronic back pain patients reported the intensity of their pain, 11 emotional states, and the corresponding body locations. These variables were used to predict pain 2 weeks later. Applying machine learning, we developed two predictive models of future pain, emphasizing interpretability. One model excluded pain-related features as predictors of future pain, and the other included pain-related predictors. The best predictors of future pain were interactive effects of (a) body maps of fatigue with negative affect and (b) positive affect with past pain. Our findings emphasize the contribution of emotions, especially emotional experience felt in the body, to understanding chronic pain above and beyond the mere tracking of pain levels. The results may contribute to the generation of a novel artificial intelligence framework to help in the development of better diagnostic and therapeutic approaches to chronic pain.

Pain perception can be studied as an inferential process in which prior information influences the perception of nociceptive input. To date, there are no suitable psychophysical paradigms to measure this at an individual level. We developed a quantitative sensory testing paradigm allowing for quantification of the influence of prior expectations versus current nociceptive input during perception. Using a Pavlovian-learning task, we investigated the influence of prior expectations on the belief about the varying strength of association between a painful electrical cutaneous stimulus and a visual cue in healthy subjects (N = 70). The belief in cue-pain associations was examined with computational modelling using a Hierarchical Gaussian Filter (HGF). Prior weighting estimates in the HGF model were compared with the established measures of conditioned pain modulation (CPM) and temporal summation of pain (TSP) assessed by cuff algometry. Subsequent HGF-modelling and estimation of the influence of prior beliefs on perception showed that 70% of subjects had a higher reliance on nociceptive input during perception of acute pain stimuli, whereas 30% showed a stronger weighting of prior expectations over sensory evidence. There was no association between prior weighting estimates and CPM or TSP. The data demonstrates relevant individual differences in prior weighting and suggests an importance of top-down cognitive processes on pain perception. Our new psychophysical testing paradigm provides a method to identify individuals with traits suggesting greater reliance on prior expectations in pain perception, which may be a risk factor for developing chronic pain and may be differentially responsive to learning-based interventions.

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue and tenderness and closely associated with high levels of stress. FMS is therefore often considered a stress-related disease. A comparative study was conducted with 99 individuals diagnosed with FMS and a control group of 50 pain-free individuals. Stress indicators were classified into three categories: perceived stress assessed using the Perceived Stress Scale, and daily average salivary cortisol and hair cortisol concentrations as indicators of acute and chronic stress levels related to the hypothalamic-pituitary-adrenal axis. Analysis of variance and covariance were used to identify group differences and the influence of covariates age, sex, and body mass index. Correlational analyses further elucidated the relationship between stress indicators and clinical symptoms. Participants with FMS reported significantly higher perceived stress levels than controls ( p  < .001, η p 2  = 0.3), which were positively correlated with symptom burden ( r  = .41, p  < .001). In contrast, there were no significant differences in the endocrinological stress indicators salivary and hair cortisol between the groups ( p  > .05), nor were these indicators associated with clinical symptoms. The study highlights the central role of perceived stress in FMS, whereas endocrinological indicators did not differentiate FMS from controls. This finding calls for a nuanced approach to clinical assessment and therapeutic interventions tailored to patients with FMS, emphasizing the management of perceived stressors.

Background The treatment of persistent fatigue after COVID-19 infection is complex. On the one hand, it involves maintaining a sufficient level of physical and mental activity to counteract possible degenerative processes of the body and nervous system. On the other hand, physical and mental activities can also lead to worsening of symptoms. Therefore, the challenge in treating Post-COVID fatigue is to stimulate the body and central nervous system in a way that stimulates growth and improvement, but does not overtax individual physical and mental limits. Special training programs try to take these characteristics into account, but often reach their limits. A promising approach is offered by new fitness technologies based on immersive virtual realities that stimulate both body and brain while minimizing physical and psychological stress. The aim of this study is to investigate the efficacy of supervised immersive Virtual Reality (VR)-based activity training compared to conventional activity training for patients with Post-COVID-associated fatigue. Methods In a single centre, individually randomised, prospective, double-blind two-arm exploratory superiority trial with parallel group design, N  = 100 patients with persistent fatigue after COVID-19 infection will be recruited. The intervention includes a supervised immersive neuromuscular training (12 sessions of 30 min over 6 weeks) based on a novel VR-exercise device. We will systematically compare the effects of this intervention on Post-COVID-associated fatigue with a supervised conventional activation program of comparable scope without an immersive environment. The primary outcome is the difference between groups in absolute change in the mean fatigue symptom severity measured on the Fatigue Severity Scale (FSS) from baseline to posttreatment assessment. Posttreatment assessment in both groups will be conducted by blinded outcome assessors. At three and six months afterwards, patients are sent self-report questionnaires for follow up. The main analysis will be based on the intention-to-treat principle. Discussion To the best of our knowledge, this is the first exploratory study on a supervised immersive neuromuscular training for the treatment of persistent fatigue after COVID-19 infection. Trial registration German register for clinical studies (ID: DRKS00032059) Prospectively registered on June 16th 2023. URL of trial registration:

[...]in recent years, enormous efforts have been made to expand the knowledge about the development and maintenance of chronic pain disorders and to improve treatment options. The research has typically focused on adults with chronic pain conditions, often neglecting to examine specific age groups that are particularly vulnerable to chronic pain or face greater challenges in managing it, such as adolescents and the elderly. [...]little is known about the specific mechanisms and characteristics of chronic pain in these age groups, which is critical for developing the most effective treatment strategies. Rev. 8, CD007407. doi: 10.1002/14651858.CD007407.pub4 Jonas Tesarz1*, Marina López-Solà2, Marta Čeko3 and Pavel Goldstein4 * 1Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany * 2Serra Hunter Program, Unit of Psychological Medicine, Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain * 3Institute of Cognitive Science, University of Colorado, Boulder, CO, United States * 4The School of Public Health, University of Haifa, Haifa, Israel

Objectives. Overlaps between different functional gastrointestinal disorders (FGIDs) are common. However, little is known about the impact of this overlap on patients’ health status. This study is aimed at analyzing the differences between patients with multiple as compared to one single FGID. Methods. A retrospective, cross-sectional study was conducted with patients presenting to a tertiary care FGID specialty clinic between 06/2012 and 01/2015 (n=294). They were characterized primarily according to their GI symptom severity (IBS-SSS) and secondarily to their physical as well as psychosocial symptom burden, quality of life, health care utilization, and work-related impairment. Differences between patients with >1 vs. 1 FGID were analyzed. Results. Of the 294 patients, 92.2% fulfilled the Rome III criteria for any FGID, and 48.0% had >1 FGIDs. FGID patients had a median age of 38 [23.0] years; 72.0% were female. Median GI symptom severity (IBS-SSS) scores were 339 [126] and 232 [163] in patients with >1 and 1 FGID, respectively (p<.001). Furthermore, patients with >1 FGIDs had higher general somatic symptom severity, higher illness anxiety, lower quality of life, and more work-related impairment. Almost no differences were found regarding their somatic as well as mental comorbidities. Conclusions. Multiple FGIDs are associated with an increased risk for complicated courses of illness as reflected in higher GI and somatic symptom severity, as well as stronger psychosocial and diet- and work-related impairment. Stepped and interdisciplinary models of care including psychosocial expertise and dietary advice are needed, especially for patients with multiple FGIDs.

Chronic noncancer pain (CNCP) is a frequent reason for counseling in general practice. Current German guidelines emphasize its biopsychosocial etiology and the importance of self-care and nonpharmacological treatment strategies such as education, physical and social activity, and psychological approaches. Comprehensive assessments are necessary to individualize treatment maximally and monitor appropriate use of pain medication. General practitioners face many challenges in implementing holistic pain management, which considers biological, psychological, and social aspects. In project RELIEF (resource-oriented case management to implement recommendations for patients with chronic pain and frequent use of analgesics in general practices), a case management program was developed to facilitate implementation of guideline recommendations on pain management regarding medical assessment and monitoring, patient and practice team education, promotion of self-care strategies, and rational pharmacotherapy. We evaluated the feasibility of the intervention and study procedures before applying them in a larger cluster randomized controlled trial. Our secondary objective is to estimate potential effects of the complex intervention. A single-arm trial with general practices and patients with CNCP and analgesics use will be conducted, accompanied by a mixed methods process evaluation. The intervention comprises 5 components, including software-supported medical pain history, 3 scheduled structured appointments, e-learning on CNCP for general practitioners and medical assistants, educational material for patients, toolbox with information on (regional) resources for patients and practice teams. Participating practices will be located in the federal state of Baden-Württemberg, Germany, and will recruit eligible patients (adults with CNCP for more than 3 months, with at least moderate pain-related disability, permanent or on-demand use of analgesics or co-analgesics in the previous 4 weeks, and practice team assessed ability to participate actively in the trial). A questionnaire given to the first 150 adult patients entering the practice in February 2025 will help screen eligible patients. The primary objective will be measured by a set of predefined indicators. The key secondary outcome is pain-related disability measured by the Pain Disability Index German version. All participants will be asked to participate in the process evaluation. Outcome evaluation data will be gathered by paper-based and digitally provided questionnaires to be completed by participants. Process evaluation data will be gathered in surveys and a qualitative study. Descriptive analyses will be performed. Recruitment occurred between October and December 2024. Targeted sample size was 6 practices and 50 patients. The intervention period will be February-June 2025. It is expected that eligible patients will benefit from the intervention and that improved medication management and intensified use of nonpharmacological treatment strategies will reduce pain-related disabilities and other patient-reported outcomes. This study will provide valuable information regarding feasibility and potential effects before testing the intervention in a confirmatory cluster randomized controlled trial. German Clinical Trials Register DRKS00034831; https://www.drks.de/search/de/trial/DRKS00034831. PRR1-10.2196/66335.

Background Childhood trauma exposures (CTEs) are frequent, well-established risk factor for the development of psychopathology. However, knowledge of the effects of CTEs in healthy individuals in a real life context, which is crucial for early detection and prevention of mental disorders, is incomplete. Here, we use ecological momentary assessment (EMA) to investigate CTE load-dependent changes in daily-life affective well-being and psychosocial risk profile in n = 351 healthy, clinically asymptomatic, adults from the community with mild to moderate CTE. Findings EMA revealed significant CTE dose-dependent decreases in real-life affective valence ( p  = 0.007), energetic arousal ( p  = 0.032) and calmness ( p  = 0.044). Psychosocial questionnaires revealed a broad CTE-related psychosocial risk profile with dose-dependent increases in mental health risk-associated features (e.g., trait anxiety, maladaptive coping, loneliness, daily hassles; p values < 0.003) and a corresponding decrease in factors protective for mental health (e.g., life satisfaction, adaptive coping, optimism, social support; p values < 0.021). These results were not influenced by age, sex, socioeconomic status or education. Conclusions Healthy community-based adults with mild to moderate CTE exhibit dose-dependent changes in well-being manifesting in decreases in affective valence, calmness and energy in real life settings, as well as a range of established psychosocial risk features associated with mental health risk. This indicates an approach to early detection, early intervention, and prevention of CTE-associated psychiatric disorders in this at-risk population, using ecological momentary interventions (EMI) in real life, which enhance established protective factors for mental health, such as green space exposure, or social support.

Abstract Objective Nonspecific chronic low back pain (CLBP) is a frequent medical condition among middle-aged and older adults. Its detrimental consequences for functional ability and quality of life are well known. However, less is known about associations of chronological age with disability and well-being among CLBP patients. Coping with pain may be harder with advancing age due to additional age-associated losses of physical, sensory, and other resources, resulting in higher disability and lower quality of life. Alternatively, older patients may feel less impaired and report higher quality of life than younger patients because the experience of chronic pain may be better anticipated and more “normative” in old age. Methods We investigated an age-heterogeneous sample of 228 CLBP patients (mean age = 59.1 years, SD = 10.2 years, range 41–82 years). Our outcomes were pain intensity, pain disability (as assessed by self-reported activity restrictions and performance-based tests), and measures of quality of life (health-related quality of life: SF-12 physical and mental health; well-being: anxiety, depression, perceived control over life, affective distress). Results Although older patients had higher performance-based disability, they scored higher on mental health and on most measures of well-being than younger patients. Conclusions Our findings provide evidence for a “paradoxical” pattern of age effects in CLBP patients and are thus in line with other studies based on nonclinical samples: Although disability in CLBP patients increases with advancing age, indicators of quality of life are equal or even higher in older patients.

Background:Chronic musculoskeletal pain (CMSP) affects between 13% and 47% of the population, with a global growth rate of 20.3% within the last 15 years, suggesting that there is a high need for effective treatments. Pain diaries have long been a common tool in nonpharmacological pain treatment for monitoring and providing feedback on patients’ symptoms in daily life. More recently, positive refocusing techniques have come to be used, promoting pain-free episodes and positive outcomes rather than focusing on managing the pain.Objective:This study aims to evaluate the feasibility (ie, acceptability, intervention adherence, and fidelity) and initial signals of efficacy of the PerPAIN app, an ecological momentary intervention for patients with CMSP. The app comprises digitalized monitoring using the experience sampling method (ESM) and feedback. In addition, the patients receive 3 microinterventions targeted at refocusing of attention on positive events.Methods:In a microrandomized trial, we will recruit 35 patients with CMSP who will be offered the app for 12 weeks. Participants will be prompted to fill out 4 ESM monitoring questionnaires a day assessing information on their current context and the proximal outcome variables: absence of pain, positive mood, and subjective activity. Participants will be randomized daily and weekly to receive no feedback, verbal feedback, or visual feedback on proximal outcomes assessed by the ESM. In addition, the app will encourage participants to complete 3 microinterventions based on positive psychology and cognitive behavioral therapy techniques. These microinterventions are prompts to report joyful moments and everyday successes or to plan pleasant activities. After familiarizing themselves with each microintervention individually, participants will be randomized daily to receive 1 of the 3 exercises or none. We will assess whether the 2 feedback types and the 3 microinterventions increase proximal outcomes at the following time point. The microrandomized trial is part of the PerPAIN randomized controlled trial (German Clinical Trials Register DRKS00022792) investigating a personalized treatment approach to enhance treatment outcomes in CMSP.Results:Approval was granted by the Ethics Committee II of the University of Heidelberg on August 4, 2020. Recruitment for the microrandomized trial began in May 2021 and is ongoing at the time of submission. By October 10, 2022, a total of 24 participants had been enrolled in the microrandomized trial.Conclusions:This trial will provide evidence on the feasibility of the PerPAIN app and the initial signals of efficacy of the different intervention components. In the next step, the intervention would need to be further refined and investigated in a definitive trial. This ecological momentary intervention presents a potential method for offering low-level accessible treatment to a wide range of people, which could have substantial implications for public health by reducing disease burden of chronic pain in the population.International Registered Report Identifier (IRRID):DERR1-10.2196/43376