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Brain-Derived Neurotrophic Factor and Immune Cells in Osteoarthritis, Chronic Low Back Pain, and Chronic Widespread Pain Patients: Association with Anxiety and Depression.

ABSTRACT: Background and Objectives: Musculoskeletal dysfunction can induce several types of chronic pain syndromes. It is of particular interest to elucidate the pathomechanism of different forms of chronic pain. It is possible that patients who have developed chronic widespread pain (CWP) may endure different pathomechanisms as compared to those who suffer from local pain (osteoarthritis, OA) and regional pain (chronic low back pain, cLBP), especially with regard to pain regulation and its related biomediators. The aim of this study was to determine the differences in pathomechanisms among these patients by measuring pain-related biomediators, particularly brain-derived neurotrophic factor (BDNF). Additionally, subpopulations of immune cells were determined in parallel. Materials and Methods: Patients and healthy subjects (HSs) were recruited (age and gender-matched). BDNF was measured from serum samples of patients and HSs and the data of body composition parameters were recorded. Additionally, both patients and HSs were asked to fill in questionnaires related to pain intensity, anxiety, and depression. Results: Our results highlight that the levels of both free and total BDNF are significantly lower in pain patients compared to HSs, with p values of 0.041 and 0.024, respectively. The number of CD3^- CD56_bright natural killer (NK) cells shows significant differences between the groups. Comparing all chronic pain patients with HSs reveals a significantly lower number of CD4⁺ CD8⁺ T cells (p = 0.031), CD3^- CD56_bright NK cells (p = 0.049) and CD20⁺ CD3^- cells (p = 0.007). Conclusions: To conclude, it seems that a general conformity between the pathomechanisms of different chronic pain diseases exists, although there are unique findings only in specific chronic pain patients.

SUBMITTER: Dimmek DJ

PROVIDER: S-EPMC8065931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cross-sectional study.To examine the sensitivity of 2 single-item questions compared with 2 longer questionnaires for screening depression and anxiety among patients with chronic low back pain (CLBP).Psychosocial factors are frequently identified as risk factors for developing CLBP and as predictors for treatment, and questionnaires are often used to screen for this. Shorter instruments may be easier to use in clinical practice settings.A total of 564 patients with 2 to 10 months of at least 50% sickness absence due to nonspecific low back pain were assessed for depression and anxiety with the Mini-International Neuropsychiatric Interview (MINI). Single-item questions for depression and anxiety from the Subjective Health Complaint Inventory and 2 longer questionnaires, the Hospital Anxiety and Depression Scale and Hopkins Symptom Checklist-25, were compared with MINI results, considered the "gold standard" in this study. Sensitivity and specificity of single-item and longer questionnaires and receiver operating characteristic curves were compared.According to MINI, the prevalence of anxiety disorders was 12% whereas that of depressive disorders was 4%. The screening questions showed 95% sensitivity and 56% specificity for depressive disorders and 68% sensitivity and 85% specificity for anxiety disorders. The longer questionnaire, Hospital Anxiety and Depression Scale, showed 91% sensitivity and 85% specificity for depressive disorders and 58% sensitivity and 83% specificity for anxiety disorders. Hopkins Symptom Checklist-25 showed 86% sensitivity and 74% specificity for depressive disorders and 67% sensitivity and 87% specificity for anxiety disorders. For 3 of the anxiety disorders and 2 of the depressive disorders, a perfect sensitivity was found between the screening questions and MINI.A single-item screening question was sensitive for depression but less sensitive for anxiety. The screening questions further performed equal to 2 widely used questionnaires. Validation of these results in other populations and compared with other short-item screeners is needed.

Project description:BackgroundThe Hospital Anxiety and Depression Scale (HADS) is one of the most popular measures of anxiety and depression. The original HADS is mostly used in Nigeria precluding people with limited literacy. This study aimed to cross-culturally adapt and psychometrically test the HADS for rural and urban Nigerian Igbo populations with chronic low back pain (CLBP) who have limited literacy.MethodsThe HADS was forward translated, back translated, and appraised. Face and content validity was ensured by pre-testing the translated measure among a convenience sample of twelve rural Nigerian dwellers with CLBP. Reliability utilising Cronbach's alpha, intraclass correlation coefficient, Bland-Altman plots and minimal detectable change were investigated amongst a convenience sample of 50 people living with CLBP in rural and urban Nigerian communities. Construct validity testing involving correlations between Igbo-HADS and Roland Morris Disability Questionnaire measuring self-reported back pain-specific disability, World Health Organisation Disability Assessment Schedule assessing generic self-reported disability, Fear Avoidance Beliefs Questionnaire measuring fear avoidance beliefs, and eleven-point box scale assessing pain intensity, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) among a random sample of 200 adults with CLBP in rural Nigerian communities were conducted.ResultsIdioms and colloquialisms were difficult to adapt. Internal consistency was good (α = 0.78) and acceptable (α = 0.67) for anxiety and depression subscales respectively. Intraclass correlation coefficients were very good (ICC ≃ 0.8) for both subscales. Minimal detectable change was 6.23 and 5.06 for anxiety and depression subscales respectively. The Igbo-HADS and the anxiety subscale had strong correlations (≃ 0.7) with generic self-reported disability; moderate correlations (≃ 0.5-0.6) with pain intensity, self-reported back pain-specific disability, and fear avoidance beliefs. The depression subscale had the lowest correlations (≃ 0.3-0.4) with these outcomes. The EFA produced a two-factor structure with cross-loading of items. The CFA showed poor fit indices for the EFA structure, the original two-factor structure, and one-factor structure.ConclusionThe HADS may not be suitable for assessing anxiety and depression, or emotional distress in this population due to difficulty achieving cross-cultural equivalence with western idioms; and the expression of emotional distress through somatisation in this culture.

Project description:BackgroundChronic low back pain is a worldwide burden that is not being abated with our current knowledge and treatment of the condition. The fear-avoidance model is used to explain the relationship between pain and disability in patients with chronic low back pain. However there are gaps in empirical support for pathways proposed within this model, and no evidence exists as to whether physical activity moderates these pathways.MethodsThis was a cross-sectional study of 218 people with chronic low back pain. Multiple mediation analyses were conducted to determine the role of fear, catastrophizing, depression, and anxiety in the relationship between pain and disability. Separate analyses were performed with physical activity as the moderator. Individuals were classified as performing regular structured physical activity if they described on average once per week for > 30-minutes an activity classified at least moderate intensity (? 4-6 METs), activity prescribed by an allied health professional for their back pain, leisure time sport or recreation, or self-directed physical activity such as resistance exercise.ResultsFear, catastrophizing, and depression significantly mediated the relationship between pain and disability (p<0.001). However the mediating effect of catastrophizing was conditional upon weekly physical activity. That is, the indirect effect for catastrophizing mediating the relationship between pain and disability was only significant for individuals reporting weekly physical activity (B = 1.31, 95% CI 0.44 to 2.23), compared to individuals reporting no weekly physical activity (B = 0.21, 95% CI -0.50 to 0.97). Catastrophizing also mediated the relationship between pain and fear (B = 0.37, 95% CI 0.15 to 0.62), with higher scores explaining 53% of the total effect of pain on fear.ConclusionsThese results support previous findings about the importance of fear and depression as factors that should be targeted in low back pain patients to reduce back pain related disability. We have also extended understanding for the mediating effect of catastrophizing on back pain related disability. Back pain patients engaged with regular physical activity may require counselling with regards to negative pain perceptions.

Project description:We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

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Brain-Derived Neurotrophic Factor and Immune Cells in Osteoarthritis, Chronic Low Back Pain, and Chronic Widespread Pain Patients: Association with Anxiety and Depression.

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