Application of the grading system for "nociplastic pain" in chronic primary and chronic secondary pain conditions: a field study.

ABSTRACT: The concept "nociplastic pain" has been developed for patients with features of nociceptive system sensitization that are not explained as nociceptive or neuropathic. Here, we tested how well the recently published grading system differentiates between chronic primary and secondary pain conditions. We recruited patients with fibromyalgia (FMS, n = 41), complex regional pain syndrome (CRPS, n = 11), osteoarthritis (OA, n = 21), or peripheral nerve injury (PNI, n = 8). We used clinical history, pain drawings, quantitative sensory testing (QST), and questionnaires to classify their pains as possibly or probably "nociplastic." All patients with chronic primary pain exhibited widespread/regional pain not explainable by either nociceptive or neuropathic mechanisms. Widespread pain occurred in 12 patients with OA but was identified as nociceptive in 11 of 12. Regional pain occurred in 4 patients with PNI but was identified as neuropathic in 3 of 4. At this step, the grading system had 100% sensitivity and 93% specificity. Clinical evidence for pain hypersensitivity by QST, and history of hypersensitivity and mental comorbidities did not differentiate between chronic primary pain (QST: 36/52 = 69%, history: 43/52 = 83%) and secondary pain conditions (QST: 20/29 = 69%, history: 24/29 83%). Based on these data, specificity remained excellent (93%), but sensitivity dropped substantially (60%) due to lacking evidence for pain hypersensitivity in many patients with FMS. This low sensitivity suggests that the published grading system is not suitable for screening purposes. We suggest structural and content modifications to improve sensitivity, including placement of patient history before clinical examination and addition of a high tender point count as evidence for widespread pain hypersensitivity.

Efficacy of supervised immersive virtual reality-based training for the treatment of chronic fatigue in post-COVID syndrome: study protocol for a double-blind randomized controlled trial (IFATICO Trial).

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.

Recalled Maternal Rearing Behaviour of Individuals Born Preterm and Their Mothers: The Impact of Intimate Mother-Child Contact.

Background: Preterm birth is a risk factor for a variety of detrimental health outcomes. Previous studies have identified recalled (or remembered) parental rearing behaviour as a potential modifier of preterm individuals' mental health in adulthood. However, no investigations to date have contrasted the parents' and children's views, explored whether their congruence is associated with preterm individuals' mental health, or tested associations with maternal self-reported first skin-on-skin contact. Methods: This cohort study involved 199 participants of the Gutenberg Prematurity Eye Study (GPES), with prospective clinical examination and psychological assessment data available for individuals born preterm and term and their mothers' perspective on recalled parental rearing behaviour. Participants also completed the Patient Health Questionnaire-9 (PHQ-9). Results: There were substantial similarities between reported recalled maternal rearing behaviour of individuals born preterm and at term and their mothers, with individuals born preterm with lower gestational age (age of the pregnancy from the woman's last menstrual period) recalling mothers as comparatively more controlling and overprotective. Incongruence in recalled rejection/punishment was associated with more depressive symptoms. Late first skin-to-skin contact was related to more recalled maternal rejection/punishment, less emotional warmth, and more control/overprotection. Conclusions: this study expands the knowledge about the interrelations of preterm birth, maternal rearing behaviour, and mental health, underscoring the relevance of first relationship experiences, including close intimate contact.

Measuring interpersonal trauma: Development and validation of the German version of the victimization experience schedule (VES).

OBJECTIVE: Interpersonal victimization experiences (VEs) significantly affect mental and physical health, particularly in disorders associated with life-time adversities, like fibromyalgia syndrome (FMS) and major depressive disorder (MDD). However, assessing VEs comprehensively remains challenging due to limited tools that encompass sub-traumatic events, such as bullying or discrimination, and contextual dimensions. We aimed to address this gap by validating the Victimization Experience Schedule (VES) in German, examining its reliability, and assessing VEs in clinical populations with FMS and MDD. METHODS: We investigated the relationship between VEs and clinical symptoms in individuals with FMS, MDD and healthy controls (N = 105) in a case-control study. We also analyzed correlations between different types of VEs and categories of early childhood abuse and posttraumatic-stress-disorder instruments. Additionally, we validated our findings in an independent sample of individuals with FMS (N = 97) from a clinical study. RESULTS: We observed excellent inter-rater reliability (Kw = 0.90-0.99), and VEs assessed using the VES were in alignment with subcategories of early childhood abuse. The prevalence of VEs extended beyond the categories covered by traditional survey instruments and was higher in individuals with MDD (4.0 ± 2.6) and FMS (5.9 ± 3.1) compared to controls (1.5 ± 1.7). We consistently identified a significant association between the number of VEs, the associated subjective distress, and clinical scores. Furthermore, distinct correlation patterns between VEs and clinical outcomes emerged across different cohorts. CONCLUSION: Our study emphasizes the VES's value in understanding VEs within MDD and FMS. These experiences span from traumatic to sub-traumatic and correlate with posttraumatic-stress and clinical symptoms, underscoring the VES's importance as an assessment tool.

Defining suffering in pain: a systematic review on pain-related suffering using natural language processing.

ABSTRACT: Understanding, measuring, and mitigating pain-related suffering is a key challenge for both clinical care and pain research. However, there is no consensus on what exactly the concept of pain-related suffering includes, and it is often not precisely operationalized in empirical studies. Here, we (1) systematically review the conceptualization of pain-related suffering in the existing literature, (2) develop a definition and a conceptual framework, and (3) use machine learning to cross-validate the results. We identified 111 articles in a systematic search of Web of Science, PubMed, PsychINFO, and PhilPapers for peer-reviewed articles containing conceptual contributions about the experience of pain-related suffering. We developed a new procedure for extracting and synthesizing study information based on the cross-validation of qualitative analysis with an artificial intelligence-based approach grounded in large language models and topic modeling. We derived a definition from the literature that is representative of current theoretical views and describes pain-related suffering as a severely negative, complex, and dynamic experience in response to a perceived threat to an individual's integrity as a self and identity as a person. We also offer a conceptual framework of pain-related suffering distinguishing 8 dimensions: social, physical, personal, spiritual, existential, cultural, cognitive, and affective. Our data show that pain-related suffering is a multidimensional phenomenon that is closely related to but distinct from pain itself. The present analysis provides a roadmap for further theoretical and empirical development.

Group eye movement desensitization and reprocessing (EMDR) in chronic pain patients.

The prevalence of chronic pain is increasing, and conventional pain therapies often have limited efficacy in individuals with high levels of psychological distress and a history of trauma. In this context, the use of Eye Movement Desensitization and Reprocessing (EMDR), an evidence-based psychotherapy approach for the treatment of posttraumatic stress disorder, is becoming increasingly important. EMDR shows promising results, particularly for patients with pain and high levels of emotional distress. Although group therapy is becoming increasingly popular in pain management, EMDR has mainly been studied as an individual treatment. However, a systematic review suggests that group therapy can be an effective tool for improving mental health outcomes, especially when trauma is addressed together. Based on these findings, an outpatient EMDR group program was developed for patients with chronic pain. The program consists of a total of four treatment days with 5-5.5 h therapy sessions each day and provides patients with a supportive environment in which they can learn effective pain management strategies and interact with other patients with similar experiences. Initial pilot evaluations indicate high efficacy and adequate safety for patients with chronic pain.

[Body, mind and culture : The complex dimensions of experiencing pain]. / Körper, Psyche und Kultur : Die komplexen Dimensionen des Schmerzerlebens.

This article deals with the interrelationship between body, mind and culture with respect to being healthy and being ill. If one wants to treat not only sickness but also sick people, it is helpful to be aware not only of the somatic and psychological dimensions of a disease but also of the "cultural" dimension of a disease. Based on personal reflections and supplemented by a focused literature search this article provides insights into how cultural influences not only affect the experience of illness but also decide how an illness is dealt with individually and socially. Furthermore, it is shown that not only being sick but also the sick body can be understood in somatic, psychological and cultural dimensions and that a distinction must be made between the body as it physically is and as it is subjectively perceived. Finally, an insight into the complexity of the somatopsychic and psychosomatic interactions is provided in order to derivatively show how mental stress can lead to physical pain and physical pain can become a mental stressor.

Effects of virtual reality on psychophysical measures of pain: superiority to imagination and nonimmersive conditions.

ABSTRACT: Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. The immersion in a VR landscape was compared with mental imagery and a nonimmersive control condition. Using a randomized within-crossover design, pressure pain detection and tolerance thresholds, spatial and temporal summation (SSP, TSP), and conditioned pain modulation (CPM) were measured in 28 individuals with chronic pain and 31 pain-free controls using phasic cuff pressure on the legs. Direct comparison between the groups showed that although individuals with pain had significantly lower pain thresholds, reduced CPM effects, and increased TSP, the VR condition had the same pain-inhibitory effect on pain thresholds as in pain-free controls. Conditioned pain modulation effects were reduced by all conditions compared with baseline. There were no significant differences between conditions and baseline for TSP and SSP. Overall, pain modulatory effects were largest for VR and smallest for imagery. These results demonstrate that immersion in a VR environment has an increasing effect on pain thresholds, reduces pain inhibition in a CPM paradigm, and has no effects on TSP. This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.

Impact of preterm birth on the onset of panic disorder in later life - Results from the Gutenberg Prematurity Study (GPS).

BACKGROUND: The present study aimed to investigate whether prematurity and perinatal stress exert long-term effects on the onset of panic disorder in later life. METHODS: From 40,189 adults born in Germany between 1969 and 2002, a study cohort (n = 427) stratified by gestational age (GA) (extremely preterm: GA < 29 weeks; very preterm: GA 29-32 weeks; moderately preterm: GA 33-36 weeks; and full-term GA ≥ 37 weeks) was selected (age 28.5 ± 8.7 years). Multivariable logistic regression analyses were conducted to investigate associations between gestational age at birth and panic disorder adjusting for age, gender, socioeconomic status, and perinatal factors. RESULTS: The prevalence of panic disorder was roughly equal in moderate to very preterm and full-term birth groups at 1.9%-3.8%. However, this rate significantly increased to 14.3% in the extreme preterm category (GA <2 9: 14.3 %, p = 0.002). In multivariable analyses, female gender and GA were independently associated with panic disorder. Adjusting for age, gender and socioeconomic status, panic disorder was associated with lower GA at birth (OR = 1.12 per week (CI95%: 1.01-1.26, p = 0.037). Whereas adjustment for nutrition status or indicators of perinatal stress had no effect, correction for the length of postnatal ICU-stay eliminated the association between preterm birth and later panic disorder. LIMITATIONS: Limitations include the small number of cases and the reliance on questionnaires to assess mental status. CONCLUSIONS: Prematurity likely increases the risk of panic disorder later in life, and the subsequent postnatal ICU-stay appears to be of critical importance. However, due to strong collinearity and other associated factors with preterm births, it remains unclear which is the primary determinant.

Elevated high sensitive C-reactive protein in fibromyalgia.

Introduction: Fibromyalgia syndrome (FMS) is a complex chronic pain condition characterized by widespread pain and tenderness, fatigue, and sleep disturbances. Currently, factors contributing to FMS are considered to be multifactorial, and the involvement of inflammatory processes is a question of debate. Objective: The aims of this study were (1) to assess whether serum concentrations of high-sensitivity C-reactive protein (hsCRP) differ between individuals diagnosed with FMS and pain-free controls, (2) to determine whether these differences are associated with clinical symptoms, and (3) to explore whether the observed differences can be explained by specific covariates such as age, weight, and smoking status. Methods: An ANOVA was applied to identify differences of hsCRP levels between FMS and pain-free controls and an analysis of covariance (ANCOVA) was performed to investigate the dependencies of hsCRP with respect to covariates. To assess the reliability of our findings, we also utilized a Bayesian robust estimation model to determine the level of confidence associated with our results. Results: The results showed that individuals with FMS had higher hsCRP levels compared to healthy controls [F(1,106) = 8.802, p < 0.001] and that higher hsCRP levels were significant correlated with a higher symptom burden (r = 0. 287, p = 0.008) and more tender points (r = 0.307, p = 0.005). Further, hsCRP levels were significantly associated with weight (η2 = 0.154, p < 0.001), but independent of age (η2 = 0.005, p = 0.42), smoking status (η2 = 0.002, p = 0.623), or gender (η2 = 0.0045, p = 0.437), which resulted in an insignificant group effect between FMS and controls (η2 = 0.029, p = 0.052), even after controlling for covariates. Conclusion: In conclusion, this study provides evidence that sub-inflammatory processes correlate with clinical symptoms, which can be partly attributed to differences in weight, but cannot be fully explained by them. Further research is needed to elucidate the mechanisms underlying the association between hsCRP and FMS and to explore the potential therapeutic implications of targeting hsCRP in the management of FMS.

Refocusing of Attention on Positive Events Using Monitoring-Based Feedback and Microinterventions for Patients With Chronic Musculoskeletal Pain in the PerPAIN Randomized Controlled Trial: Protocol for a Microrandomized Trial.

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.

Recalled parental rearing behavior shapes mental health after preterm birth: Evidence from the Gutenberg Prematurity Study.

Associations of preterm birth with later-life mental distress are well-established. A research gap concerns the role of psychosocial factors such as the family context. This study investigated associations of recalled parental rearing behavior with both preterm birth characteristics and psychological symptom burden later in life. Based on birth registry data of the Mainz University Hospital in Germany (infants born between 1969 and 2002) and using a selection algorithm, a cohort study comprising four gestational age (GA) strata was conducted (≥ 37 weeks: n = 138; 33-36 weeks: n = 132; 29-32 weeks: n = 106; ≤ 28 weeks: n = 132). Participants underwent a medical examination and completed standardized questionnaires. We investigated differences in dimensions of recalled parental rearing behavior according to GA and tested pre-/perinatal stress indicators and recalled parental rearing behavior as statistical predictors of depression and anxiety symptoms later in life. Lower GA was associated with more recalled emotional warmth and overprotection. Recalled emotional warmth was associated with fewer depression and anxiety symptoms, while recalled overprotection co-occurred with more depression symptoms. The findings indicate the relevance of parental rearing behavior for the offspring's mental health. As preterm birth implicates stress for the whole family requiring adaptive parental behavior, the latter could be an important modifiable risk factor.

Clinical Phenomenology of Fibromyalgia Syndrome in Male Patients: Same But Different.

The majority of knowledge about fibromyalgia syndrome (FMS) derives from studies of female patients. Little is known about the clinical characteristics and treatment outcomes of male patients with FMS. In this retrospective cohort study with a prospective posttreatment follow-up, we investigated whether male patients with FMS differ from female patients in terms of 1) symptom burden, 2) psychological characteristics, and 3) clinical treatment response. We identified 263 male (4%) out of 5,541 patients with FMS completing a 3-week multimodal pain-treatment program. Male patients (51.3 ± 9.1 years) were age- and time-matched (1:4) with female patients (N = 1,052, 51.3 ± 9.0 years). Data on clinical characteristics, psychological comorbidities, and treatment responses were obtained from medical records and validated questionnaires. Levels of perceived pain, psychological comorbidity, and functional capacity were similar between genders, although male patients with FMS showed a higher prevalence of alcohol abuse. Compared to female patients, male patients experienced themselves less often as overly accommodating (Cohen's d = -.42) but more often as self-sacrificing (d = .26) or intrusive (d = .23). Regarding pain coping, male patients were less likely to utilize mental distraction, rest- and relaxation techniques, or counteractive activities (d = .18-.27). Male patients showed a slightly worse overall response rate than women (69% vs 77%), although differences between individual outcome measures were small (d < .2). Although male and female patients in our cohort were similar in clinical presentation and treatment response, the gender-specific differences in interpersonal problems and pain coping suggest consideration of these aspects in the treatment of male patients with FMS. PERSPECTIVE: Knowledge about fibromyalgia mostly derives from studies of female patients. Identifying and understanding gender-specific differences in fibromyalgia is an important roadmap in the treatment of this syndrome by focusing on specific gender aspects such as differences in interpersonal problems and pain coping mechanisms.

2MDR, a Microcomputer-Controlled Visual Stimulation Device for Psychotherapy-Like Treatments of Mice.

Post-traumatic stress disorder and other mental disorders can be treated by an established psychotherapy called Eye Movement Desensitization and Reprocessing (EMDR). In EMDR, patients are confronted with traumatic memories while they are stimulated with alternating bilateral stimuli (ABS). How ABS affects the brain and whether ABS could be adapted to different patients or mental disorders is unknown. Interestingly, ABS reduced conditioned fear in mice. Yet, an approach to systematically test complex visual stimuli and compare respective differences in emotional processing based on semiautomated/automated behavioral analysis is lacking. We developed 2MDR (MultiModal Visual Stimulation to Desensitize Rodents), a novel, open-source, low-cost, customizable device that can be integrated in and transistor-transistor logic (TTL) controlled by commercial rodent behavioral setups. 2MDR allows the design and precise steering of multimodal visual stimuli in the head direction of freely moving mice. Optimized videography allows semiautomatic analysis of rodent behavior during visual stimulation. Detailed building, integration, and treatment instructions along with open-source software provide easy access for inexperienced users. Using 2MDR, we confirmed that EMDR-like ABS persistently improves fear extinction in mice and showed for the first time that ABS-mediated anxiolytic effects strongly depend on physical stimulus properties such as ABS brightness. 2MDR not only enables researchers to interfere with mouse behavior in an EMDR-like setting, but also demonstrates that visual stimuli can be used as a noninvasive brain stimulation to differentially alter emotional processing in mice.

How symptoms of simple acute infections affect the SSS-8 and SSD-12 as screening instruments for somatic symptom disorder in the primary care setting.

Objective: Somatic symptom disorder (SSD) is one of the most common reasons for consultations in primary care, in addition to simple acute infections. Questionnaire-based screening instruments to identify patients at high risk of SSD are thus of great clinical relevance. Although screening instruments are frequently used, it is currently unclear to what extent they are influenced by the concurrent presence of simple acute infections. Therefore, this study aimed to investigate how symptoms of simple acute infections affect the two established questionnaires as screening instruments for somatic symptom disorder in the primary care setting. Methods: In our cross-sectional, multicenter design, a total of 1,000 patients in primary care practices were screened using the two most established SSD screening questionnaires, the 8-item Somatic Symptom Scale (SSS-8) and the 12-item Somatic Symptom Disorder-B Criteria Scale (SSD-12), followed by clinical assessment by the primary care physician. Results: A total of 140 patients with a simple acute infection (acute infection group, AIG) and 219 patients with chronic somatic symptoms (somatic symptom group, SSG) were included. The patients in the SSG showed higher total SSS-8 and SSD-12 scores than the patients in the AIG; however, the SSS-8 was more susceptible to changes triggered by symptoms of a simple acute infection than the SSD-12. Conclusion: These results suggest that the SSD-12 is less susceptible to symptoms of a simple acute infection. Its total score and corresponding cutoff value provide a more specific and thus less susceptible screening tool for identifying SSD in primary care.