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Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
The genesis of chronic pain is explained by a biopsychosocial model. It hypothesizes an interdependency between environmental and genetic factors provoking aberrant long-term changes in biological and psychological regulatory systems. Physiological effects of psychological and physical stressors may play a crucial role in these maladaptive processes. Specifically, long-term demands on the stress response system may moderate central pain processing and influence descending serotonergic and noradrenergic signals from the brainstem, regulating nociceptive processing at the spinal level. However, the underlying mechanisms of this pathophysiological interplay still remain unclear. This paper aims to shed light on possible pathways between physical (exercise) and psychological stress and the potential neurobiological consequences in the genesis and treatment of chronic pain, highlighting evolving concepts and promising research directions in the treatment of chronic pain. Two treatment forms (exercise and mindfulness-based stress reduction as exemplary therapies), their interaction, and the dose-response will be discussed in more detail, which might pave the way to a better understanding of alterations in the pain matrix and help to develop future prevention and therapeutic concepts
Decades of research have demonstrated that physical stress (PS) stimulates bone remodeling and affects bone structure and function through complex mechanotransduction mechanisms. Recent research has laid ground to the hypothesis that mental stress (MS) also influences bone biology, eventually leading to osteoporosis and increased bone fracture risk. These effects are likely exerted by modulation of hypothalamic–pituitary–adrenal axis activity, resulting in an altered release of growth hormones, glucocorticoids and cytokines, as demonstrated in human and animal studies. Furthermore, molecular cross talk between mental and PS is thought to exist, with either synergistic or preventative effects on bone disease progression depending on the characteristics of the applied stressor. This mini review will explain the emerging concept of MS as an important player in bone adaptation and its potential cross talk with PS by summarizing the current state of knowledge, highlighting newly evolving notions (such as intergenerational transmission of stress and its epigenetic modifications affecting bone) and proposing new research directions.
Background: The back pain screening tool Risk-Prevention-Index Social (RPI-S) identifies the individual psychosocial risk for low back pain chronification and supports the allocation of patients at risk in additional multidisciplinary treatments. The study objectives were to evaluate (1) the prognostic validity of the RPI-S for a 6-month time frame and (2) the clinical benefit of the RPI-S.
Methods: In a multicenter single-blind 3-armed randomized controlled trial, n = 660 persons (age 18–65 years) were randomly assigned to a twelve-week uni- or multidisciplinary exercise intervention or control group. Psychosocial risk was assessed by the RPI-S domain social environment (RPI-SSE) and the outcome pain by the Chronic Pain Grade Questionnaire (baseline M1, 12-weeks M4, 24-weeks M5). Prognostic validity was quantified by the root mean squared error (RMSE) within the control group. The clinical benefit of RPI-SSE was calculated by repeated measures ANOVA in intervention groups.
Results: A subsample of n = 274 participants (mean = 38.0 years, SD 13.1) was analyzed, of which 30% were classified at risk in their psychosocial profile. The half-year prognostic validity was good (RMSE for disability of 9.04 at M4 and of 9.73 at M5; RMSE for pain intensity of 12.45 at M4 and of 14.49 at M5). People at risk showed significantly stronger reduction in pain disability and intensity at M4/M5, if participating in a multidisciplinary exercise treatment. Subjects at no risk showed a smaller reduction in pain disability in both interventions and no group differences for pain intensity. Regarding disability due to pain, around 41% of the sample would gain an unfitted treatment without the back pain screening.
Conclusion: The RPI-SSE prognostic validity demonstrated good applicability and a clinical benefit confirmed by a clear advantage of an individualized treatment possibility.
Introduction: Chronic low back pain (LBP) is a major cause of disability; early diagnosis and stratification of care remain challenges.
Objectives: This article describes the development of a screening tool for the 1-year prognosis of patients with high chronic LBP risk (risk stratification index) and for treatment allocation according to treatment-modifiable yellow flag indicators (risk prevention indices, RPI-S).
Methods: Screening tools were derived from a multicentre longitudinal study (n = 1071, age >18, intermittent LBP). The greatest prognostic predictors of 4 flag domains ("pain," "distress," "social-environment," "medical care-environment") were determined using least absolute shrinkage and selection operator regression analysis. Internal validity and prognosis error were evaluated after 1-year follow-up. Receiver operating characteristic curves for discrimination (area under the curve) and cutoff values were determined.
Results: The risk stratification index identified persons with increased risk of chronic LBP and accurately estimated expected pain intensity and disability on the Pain Grade Questionnaire (0-100 points) up to 1 year later with an average prognosis error of 15 points. In addition, 3-risk classes were discerned with an accuracy of area under the curve = 0.74 (95% confidence interval 0.63-0.85). The RPI-S also distinguished persons with potentially modifiable prognostic indicators from 4 flag domains and stratified allocation to biopsychosocial treatments accordingly.
Conclusion: The screening tools, developed in compliance with the PROGRESS and TRIPOD statements, revealed good validation and prognostic strength. These tools improve on existing screening tools because of their utility for secondary preventions, incorporation of exercise effect modifiers, exact pain estimations, and personalized allocation to multimodal treatments.
Background Low back pain (LBP) is a common pain syndrome in athletes, responsible for 28% of missed training days/year. Psychosocial factors contribute to chronic pain development. This study aims to investigate the transferability of psychosocial screening tools developed in the general population to athletes and to define athlete-specific thresholds.
Methods Data from a prospective multicentre study on LBP were collected at baseline and 1-year follow-up (n=52 athletes, n=289 recreational athletes and n=246 non-athletes). Pain was assessed using the Chronic Pain Grade questionnaire. The psychosocial Risk Stratification Index (RSI) was used to obtain prognostic information regarding the risk of chronic LBP (CLBP). Individual psychosocial risk profile was gained with the Risk Prevention Index – Social (RPI-S). Differences between groups were calculated using general linear models and planned contrasts. Discrimination thresholds for athletes were defined with receiver operating characteristics (ROC) curves.
Results Athletes and recreational athletes showed significantly lower psychosocial risk profiles and prognostic risk for CLBP than non-athletes. ROC curves suggested discrimination thresholds for athletes were different compared with non-athletes. Both screenings demonstrated very good sensitivity (RSI=100%; RPI-S: 75%–100%) and specificity (RSI: 76%–93%; RPI-S: 71%–93%). RSI revealed two risk classes for pain intensity (area under the curve (AUC) 0.92(95% CI 0.85 to 1.0)) and pain disability (AUC 0.88(95% CI 0.71 to 1.0)).
Conclusions Both screening tools can be used for athletes. Athlete-specific thresholds will improve physicians’ decision making and allow stratified treatment and prevention.
Stress and pain
(2022)
Introduction: Low back pain (LBP) leads to considerable impairment of quality of life worldwide and is often accompanied by psychosomatic symptoms.
Objectives: First, to assess the association between stress and chronic low back pain (CLBP) and its simultaneous appearance with fatigue and depression as a symptom triad. Second, to identify the most predictive stress-related pattern set for CLBP for a 1-year diagnosis.
Methods: In a 1-year observational study with four measurement points, a total of 140 volunteers (aged 18–45 years with intermittent pain) were recruited. The primary outcomes were pain [characteristic pain intensity (CPI), subjective pain disability (DISS)], fatigue, and depressive mood. Stress was assessed as chronic stress, perceived stress, effort reward imbalance, life events, and physiological markers [allostatic load index (ALI), hair cortisol concentration (HCC)]. Multiple linear regression models and selection procedures for model shrinkage and variable selection (least absolute shrinkage and selection operator) were applied. Prediction accuracy was calculated by root mean squared error (RMSE) and receiver-operating characteristic curves.
Results: There were 110 participants completed the baseline assessments (28.2 7.5 years, 38.1% female), including HCC, and a further of 46 participants agreed to ALI laboratory measurements. Different stress types were associated with LBP, CLBP, fatigue, and depressive mood and its joint occurrence as a symptom triad at baseline; mainly social-related stress types were of relevance. Work-related stress, such as “excessive demands at work”[b = 0.51 (95%CI -0.23, 1.25), p = 0.18] played a role for upcoming chronic pain disability. “Social overload” [b = 0.45 (95%CI -0.06, 0.96), p = 0.080] and “over-commitment at work” [b = 0.28 (95%CI -0.39, 0.95), p = 0.42] were associated with an upcoming depressive mood within 1-year. Finally, seven psychometric (CPI: RMSE = 12.63; DISS: RMSE = 9.81) and five biomarkers (CPI: RMSE = 12.21; DISS: RMSE = 8.94) could be derived as the most predictive pattern set for a 1-year prediction of CLBP. The biomarker set showed an apparent area under the curve of 0.88 for CPI and 0.99 for DISS.
Conclusion: Stress disrupts allostasis and favors the development of chronic pain, fatigue, and depression and the emergence of a “hypocortisolemic symptom triad,” whereby the social-related stressors play a significant role. For translational medicine, a predictive pattern set could be derived which enables to diagnose the individuals at higher risk for the upcoming pain disorders and can be used in practice.
The effects of exercise interventions on unspecific chronic low back pain (CLBP) have been investigated in many studies, but the results are inconclusive regarding exercise types, efficiency, and sustainability. This may be because the influence of psychosocial factors on exercise induced adaptation regarding CLBP is neglected. Therefore, this study assessed psychosocial characteristics, which moderate and mediate the effects of sensorimotor exercise on LBP. A single-blind 3-arm multicenter randomized controlled trial was conducted for 12-weeks. Three exercise groups, sensorimotor exercise (SMT), sensorimotor and behavioral training (SMT-BT), and regular routines (CG) were randomly assigned to 662 volunteers. Primary outcomes (pain intensity and disability) and psychosocial characteristics were assessed at baseline (M1) and follow-up (3/6/12/24 weeks, M2-M5). Multiple regression models were used to analyze whether psychosocial characteristics are moderators of the relationship between exercise and pain, meaning that psychosocial factors and exercise interact. Causal mediation analysis were conducted to analyze, whether psychosocial characteristics mediate the exercise effect on pain. A total of 453 participants with intermittent pain (mean age = 39.5 ± 12.2 years, f = 62%) completed the training. It was shown, that depressive symptomatology (at M4, M5), vital exhaustion (at M4), and perceived social support (at M5) are significant moderators of the relationship between exercise and the reduction of pain intensity. Further depressive mood (at M4), social-satisfaction (at M4), and anxiety (at M5 SMT) significantly moderate the exercise effect on pain disability. The amount of moderation was of clinical relevance. In contrast, there were no psychosocial variables which mediated exercise effects on pain. In conclusion it was shown, that psychosocial variables can be moderators in the relationship between sensorimotor exercise induced adaptation on CLBP which may explain conflicting results in the past regarding the merit of exercise interventions in CLBP. Results suggest further an early identification of psychosocial risk factors by diagnostic tools, which may essential support the planning of personalized exercise therapy.
Level of Evidence: Level I.
Clinical Trial Registration: DRKS00004977, LOE: I, MiSpEx: grant-number: 080102A/11-14. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004977.
Objectives: Chronic back pain (CBP) can lead to disability and burden. In addition to its medical causes, its development is influenced by psychosocial risk factors, the so-called flag factors, which are categorized and integrated into many treatment guidelines. Currently, most studies investigate single flag factors, which limit the estimation of individual factor significance in the development of chronic pain. Furthermore, factors concerning patients’ lifestyle, biography and treatment history are often neglected. Therefore, the objectives of the present study are to identify commonly neglected factors of CBP and integrate them into an analysis model comparing their significance with established flag factors.
Methods: A total of 24 patients and therapists were cross-sectionally interviewed to identify commonly neglected factors of CBP. Subsequently, the impact of these factors was surveyed in a longitudinal study. In two rehabilitation clinics, CBP patients (n = 145) were examined before and 6 months after a 3-week inpatient rehabilitation. Outcome variables, chronification factor pain experience (CF-PE) and chronification factor disability (CF-D), were ascertained with confirmatory factor analysis (CFA) of standardized questionnaires. Predictors were evaluated using stepwise calculations of simple and multiple regression models.
Results: Through interviews, medical history, iatrogenic factors, poor compliance, critical life events (LEs), social support (SS) type and effort–reward were identified as commonly neglected factors. However, only the final three held significance in comparison to established factors such as depression and pain-related cognitions. Longitudinally, lifestyle factors found to influence future pain were initial pain, physically demanding work, nicotine consumption, gender and rehabilitation clinic. LEs were unexpectedly found to be a strong predictor of future pain, as were the protective factors, reward at work and perceived SS.
Discussion: These findings shed insight regarding often overlooked factors in the development of CBP, suggesting that more detailed operationalization and superordinate frameworks would be beneficial to further research.
Conclusion: In particular, LEs should be taken into account in future research. Protective factors should be integrated in therapeutic settings.
Background
Doping presents a potential health risk for young athletes. Prevention programs are intended to prevent doping by educating athletes about banned substances. However, such programs have their limitations in practice. This led Germany to introduce the National Doping Prevention Plan (NDPP), in hopes of ameliorating the situation among young elite athletes. Two studies examined 1) the degree to which the NDPP led to improved prevention efforts in elite sport schools, and 2) the extent to which newly developed prevention activities of the national anti-doping agency (NADA) based on the NDPP have improved knowledge among young athletes within elite sports schools.
Methods
The first objective was investigated in a longitudinal study (Study I: t0 = baseline, t1 = follow-up 4 years after NDPP introduction) with N = 22 teachers engaged in doping prevention in elite sports schools. The second objective was evaluated in a cross-sectional comparison study (Study II) in N = 213 elite sports school students (54.5 % male, 45.5 % female, age M = 16.7 ± 1.3 years (all students had received the improved NDDP measure in school; one student group had received additionally NADA anti-doping activities and a control group did not). Descriptive statistics were calculated, followed by McNemar tests, Wilcoxon tests and Analysis of Covariance (ANCOVA).
Results
Results indicate that 4 years after the introduction of the NDPP there have been limited structural changes with regard to the frequency, type, and scope of doping prevention in elite sport schools. On the other hand, in study II, elite sport school students who received further NADA anti-doping activities performed better on an anti-doping knowledge test than students who did not take part (F(1, 207) = 33.99, p <0.001), although this difference was small.
Conclusion
The integration of doping-prevention in elite sport schools as part of the NDPP was only partially successful. The results of the evaluation indicate that the introduction of the NDPP has contributed more to a change in the content of doping prevention activities than to a structural transformation in anti-doping education in elite sport schools. Moreover, while students who did receive additional education in the form of the NDPP“booster sessions” had significantly more knowledge about doping than students who did not receive such education, this difference was only small and may not translate to actual behavior.