An interdisciplinary multimodal integrative healthcare program for chronic spinal pain and comorbid mental disorders.

OBJECTIVE: Previous studies evaluating interdisciplinary multimodal interventions for chronic spinal pain often excluded patients with comorbid mental disorders. This study aims to assess the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program for individuals experiencing co-occurring chronic spinal pain and mental disorders. METHODS: Participants were 944 patients with chronic spinal pain and comorbid mental disorders. Primary outcomes were Health-Related Quality of Life, assessed using the Research and Development-36 (RAND-36), and pain-related disability, assessed using the Quebec Back Pain Disability Scale (QBPDS). Secondary outcomes included pain intensity, pain catastrophizing, kinesiophobia, fatigue, lumbar mobility and isometric strength. Data was collected during the healthcare program at four time points: pre-treatment (T0), midway through 20-week treatment (T1), end of 20-week treatment (T2), and at completion of 12-month relapse prevention program (T3). Multilevel regression analyses were conducted to examine the effects of the healthcare program on primary outcomes over time. RESULTS: The 20-week treatment period yielded significant improvements in both mental (B = 0.44, t(943) = 19.42, p < 0.001) and physical component summary scores (B = 0.45, t(943) = 18.24, p < 0.001) of the RAND-36, as well as in QBPDS total score (B = -0.77, t(943) = -26.16 p < 0.001). Pre-treatment scores indicated the presence of problematic fatigue, kinesiophobia, and clinical levels of pain catastrophizing, all of which resolved by the end of the 12-month relapse prevention program. CONCLUSIONS: An interdisciplinary multimodal integrative healthcare program seems effective for patients with chronic spinal pain and comorbid mental disorders.

Clinically assessed lumbopelvic sensorimotor control tests in low back pain: are they actually valid? A systematic review according to COSMIN guidelines.

BACKGROUND: Impairments in lumbopelvic sensorimotor control (SMC) are thought to be one of the underlying mechanisms for the recurrence and persistence of low back pain (LBP). As such, lumbopelvic SMC tests are frequently included in the clinical examination of patients with LBP. OBJECTIVE: To evaluate convergent and known-groups validity of clinically assessed lumbopelvic SMC tests in patients with LBP according to COSMIN guidelines. DESIGN: Systematic review METHODS: Five electronic databases were searched until December 2023. Studies examining convergent or known-groups validity of lumbopelvic SMC tests assessed via inspection or palpation in patients with LBP were included. Known-groups validity had to be assessed between patients with LBP and pain-free persons. Two independent researchers appraised risk of bias and quality of evidence (QoE) using the COSMIN Risk of Bias checklist and modified GRADE approach, respectively. Results for known-groups validity were reported separately for single tests and test-clusters. RESULTS: Twelve studies (946 participants) were included. Three studies investigated convergent validity of three single tests. Regarding known-groups validity, six studies evaluated six single tests and four studies investigated two test-clusters. For only one test, both convergent and known-groups were assessed. The QoE for tests showing sufficient convergent or known-groups validity was (very) low, whereas QoE was moderate for single tests or test-clusters with insufficient known-groups validity. CONCLUSION: All clinically assessed lumbopelvic SMC tests with sufficient convergent or known-groups validity had (very) low QoE. Therefore, test outcomes should be interpreted cautiously and strong reliance on these outcomes for clinical decision-making can currently not be recommended.

Does movement preparation enhance attending to bodily sensations in the back in people with persistent low back pain?

Attention has been proposed to play an important role in persisting pain, with excessive attentional processes towards pain information leading to worse pain outcomes and maladaptive behaviors. Nevertheless, research on somatosensory attending during the anticipation of pain-related movements is still scarce. This study investigated if individuals with chronic and recurrent lower back pain compared to pain-free controls, show enhanced attending to somatosensory information in the back while anticipating back-recruiting movements. 43 healthy control, 33 recurrent (RLBP) and 33 chronic low back (CLBP) pain sufferers were asked to perform back-recruiting movements. Before the movement initiation cue, a task-irrelevant tactile stimulus was administered to participants' lower back to elicit somatosensory evoked potentials (SEPs), used as an index of somatosensory attending. In contrast to our hypothesis, most identified SEP components did not differ across groups. The only exception was the P175 amplitude which was larger for the CLBP group compared to individuals with RLBP and healthy controls. The current study did not find robust evidence of enhanced somatosensory attending to the back in people with persisting lower back pain. The finding that CLBP, but not RLBP individuals, had larger amplitudes to the P175 component, is discussed as possibly reflecting a higher state of emotional arousal in these patients when having to prepare the back-recruiting movements.

Influence of sensory retraining on cortical reorganization in peripheral neuropathy: A systematic review.

OBJECTIVE: This study systematically reviewed the literature about sensory retraining effect in comparison to other rehabilitative techniques on cortical reorganization in patients with peripheral neuropathic pain. TYPE: Systematic review. LITERATURE SURVEY: After performing an electronic search of PubMed, Web of Science, and Embase, risk of bias was assessed using the revised Cochrane risk of bias tool for randomized controlled trials and the risk of bias in non-randomized studies-of interventions for non-randomized studies of intervention. METHODOLOGY: The strength of conclusion was determined using the evidence-based guideline development approach. SYNTHESIS: Limited evidence indicates a higher increase in cortical inhibition and a higher reduction in cortical activation during a motor task of the affected hemisphere after graded motor imagery compared to wait-list. Higher reductions in map volume (total excitability of the cortical representation) of the affected hemisphere after peripheral electrical stimulation (PES) were observed when compared to transcranial direct current stimulation (tDCS) or to sham treatment with limited evidence. No other differences in cortical excitability and representation of the affected and non-affected hemisphere were observed when comparing mirror therapy with sham therapy or tDCS, PES with sham therapy or tDCS, and graded motor imagery with wait-list. CONCLUSIONS: Graded motor imagery and PES result in higher cortical excitability reductions of the affected hemisphere compared to wait-list, tDCS and sham treatment, respectively.

Evidence- and data-driven classification of low back pain via artificial intelligence: Protocol of the PREDICT-LBP study.

In patients presenting with low back pain (LBP), once specific causes are excluded (fracture, infection, inflammatory arthritis, cancer, cauda equina and radiculopathy) many clinicians pose a diagnosis of non-specific LBP. Accordingly, current management of non-specific LBP is generic. There is a need for a classification of non-specific LBP that is both data- and evidence-based assessing multi-dimensional pain-related factors in a large sample size. The "PRedictive Evidence Driven Intelligent Classification Tool for Low Back Pain" (PREDICT-LBP) project is a prospective cross-sectional study which will compare 300 women and men with non-specific LBP (aged 18-55 years) with 100 matched referents without a history of LBP. Participants will be recruited from the general public and local medical facilities. Data will be collected on spinal tissue (intervertebral disc composition and morphology, vertebral fat fraction and paraspinal muscle size and composition via magnetic resonance imaging [MRI]), central nervous system adaptation (pain thresholds, temporal summation of pain, brain resting state functional connectivity, structural connectivity and regional volumes via MRI), psychosocial factors (e.g. depression, anxiety) and other musculoskeletal pain symptoms. Dimensionality reduction, cluster validation and fuzzy c-means clustering methods, classification models, and relevant sensitivity analyses, will classify non-specific LBP patients into sub-groups. This project represents a first personalised diagnostic approach to non-specific LBP, with potential for widespread uptake in clinical practice. This project will provide evidence to support clinical trials assessing specific treatments approaches for potential subgroups of patients with non-specific LBP. The classification tool may lead to better patient outcomes and reduction in economic costs.

Towards data-driven biopsychosocial classification of non-specific chronic low back pain: a pilot study.

The classification of non-specific chronic low back pain (CLBP) according to multidimensional data could guide clinical management; yet recent systematic reviews show this has not been attempted. This was a prospective cross-sectional study of participants with CLBP (n = 21) and age-, sex- and height-matched pain-free controls (n = 21). Nervous system, lumbar spinal tissue and psychosocial factors were collected. Dimensionality reduction was followed by fuzzy c-means clustering to determine sub-groups. Machine learning models (Support Vector Machine, k-Nearest Neighbour, Naïve Bayes and Random Forest) were used to determine the accuracy of classification to sub-groups. The primary analysis showed that four factors (cognitive function, depressive symptoms, general self-efficacy and anxiety symptoms) and two clusters (normal versus impaired psychosocial profiles) optimally classified participants. The error rates in classification models ranged from 4.2 to 14.2% when only CLBP patients were considered and increased to 24.2 to 37.5% when pain-free controls were added. This data-driven pilot study classified participants with CLBP into sub-groups, primarily based on psychosocial factors. This contributes to the literature as it was the first study to evaluate data-driven machine learning CLBP classification based on nervous system, lumbar spinal tissue and psychosocial factors. Future studies with larger sample sizes should validate these findings.

An interdisciplinary multimodal integrative healthcare program for depressive and anxiety disorders.

Objective: Although multimodal interventions are recommended in patients with severe depressive and/or anxiety disorders, available evidence is scarce. Therefore, the current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, for patients with (comorbid) depressive and/or anxiety disorders. Methods: Participants were 3,900 patients diagnosed with a depressive and/or anxiety disorder. The primary outcome was Health-Related Quality of Life (HRQoL) measured with the Research and Development-36 (RAND-36). Secondary outcomes included: (1) current psychological and physical symptoms measured with the Brief Symptom Inventory (BSI) and (2) symptoms of depression, anxiety, and stress measured with the Depression Anxiety Stress Scale (DASS). The healthcare program consisted of two active treatment phases: main 20-week program and a subsequent continuation-phase intervention (i.e., 12-month relapse prevention program). Mixed linear models were used to examine the effects of the healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of 12-month relapse prevention program (T3). Results: Results showed significant improvements from T0 to T2 for the primary variable (i.e., RAND-36) and secondary variables (i.e., BSI/DASS). During the 12-month relapse prevention program, further significant improvements were mainly observed for secondary variables (i.e., BSI/DASS) and to a lesser extent for the primary variable (i.e., RAND-36). At the end of the relapse prevention program (i.e., T3), 63% of patients achieved remission of depressive symptoms (i.e., DASS depression score ≤ 9) and 67% of patients achieved remission of anxiety symptoms (i.e., DASS anxiety score ≤ 7). Conclusion: An interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, seems effective for patients suffering from depressive and/or anxiety disorders with regard to HRQoL and symptoms of psychopathology. As reimbursement and funding for interdisciplinary multimodal interventions in this patient group has been under pressure in recent years, this study could add important evidence by reporting on routinely collected outcome data from a large patient group. Future studies should further investigate the long-term stability of treatment outcomes after interdisciplinary multimodal interventions for patients suffering from depressive and/or anxiety disorders.

Sensory Profiling in Classical Ehlers-Danlos Syndrome: A Case-Control Study Revealing Pain Characteristics, Somatosensory Changes, and Impaired Pain Modulation.

Pain is one of the most important yet poorly understood complaints in heritable connective tissue disorders (HCTDs) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for the Ehlers-Danlos syndrome (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (Visual Analogue Scale ≥5/10 in 32% for average pain intensity the past month) and worse health-related quality of life. An altered somatosensory profile was found in the cEDS group with higher (P = .04) detection thresholds for vibration stimuli at the lower limb, indicating hypoesthesia, reduced thermal sensitivity with more (P < .001) paradoxical thermal sensations (PTSs), and hyperalgesia with lower pain thresholds to mechanical (P < .001) stimuli at both the upper and lower limbs and cold (P = .005) stimulation at the lower limb. Using a parallel conditioned pain modulation paradigm, the cEDS group showed significantly smaller antinociceptive responses (P-value .005-.046) suggestive of impaired endogenous pain modulation. In conclusion, individuals with cEDS report chronic pain and worse health-related quality of life and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights into the possible role of the ECM in the development and persistence of pain. PERSPECTIVE: Chronic pain compromises the quality of life in individuals with cEDS. Moreover, an altered somatosensory perception was found in the cEDS group with hypoesthesia for vibration stimuli, more PTSs, hyperalgesia for pressure stimuli, and impaired pain modulation.

Sensory profiling in classical Ehlers-Danlos syndrome: a case-control study revealing pain characteristics, somatosensory changes, and impaired pain modulation.

Pain is one of the most important, yet poorly understood complaints in heritable connective tissue disorders (HCTD) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for Ehlers-Danlos syndromes (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (VAS ≥5/10 in 32% for average pain intensity the past month) and worse health -related quality of life. Altered sensory profile was found in the cEDS group with higher (p=0.04) detection thresholds for vibration stimuli at the lower limb indicating hypoesthesia, reduced thermal sensitivity with more (p<0.001) paradoxical thermal sensations, and hyperalgesia with lower pain thresholds to mechanical (p<0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb. Using a parallel conditioned pain paradigm, the cEDS group showed significantly smaller antinociceptive responses (p-value between 0.005 and 0.046) suggestive of impaired endogenous central pain modulation. In conclusion, Individuals with cEDS report chronic pain and worse health-related quality of life, and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights on the possible role of the ECM in the development and persistence of pain.

The Interaction Between Psychosocial Factors and Exercise-Induced Hypoalgesia in Pain-Free Nurses.

Purpose: This cross-sectional study aimed to investigate whether psychosocial factors were predictive for exercise-induced hypoalgesia (EIH) in pain-free adults. Methods: A sample of 38 pain-free nurses with a mean (SD) age of 26 (6) years were included in this study. Participants completed psychosocial questionnaires prior to physical tests. Pressure pain threshold (PPT) was assessed bilaterally at the calves (local), lower back (semi-local) and forearm (remote) before and immediately after a maximal graded cycling exercise test. Separate linear mixed effects models were used to determine change in PPT before and after cycling exercise (EIH). Multiple linear regression for all psychosocial variables and best subset regression was used to identify predictors of EIH at all locations. Results: The relative mean increase in PPT at the forearm, lumbar, calf, and globally (all sites pooled) was 6.0% (p<0.001), 10.1% (p<0.001), 13.9% (p<0.001), and 10.2% (p=0.013), respectively. Separate best subset multiple linear regression models at the forearm (predictors; Multidimensional Scale of Perceived Social Support (MSPSS) total), lumbar (predictors; MSPSS total, Pain Catastrophizing Scale (PCS) total, Depression Anxiety Stress Scale (DASS) depression), calf (predictors; MSPSS friends, PCS total), and global (predictors; MSPSS friends, PCS total) accounted for 7.5% (p=0.053), 13% (p=0.052), 24% (p=0.003), and 17% (p=0.015) of the variance, respectively. Conclusion: These findings confirm that cycling exercise produced EIH in young nurses and provided preliminary evidence to support the interaction between perceived social support, pain catastrophizing and EIH. Further investigation is required to better understand psychological and social factors that mediate EIH on a larger sample of adults at high risk of developing chronic musculoskeletal pain.

An interdisciplinary multimodal integrative healthcare program for somatic symptom disorder, with predominant (spinal) pain.

OBJECTIVE: Although multimodal interventions are generally recommended in patients with long-term somatic symptom disorders (SSD), available evidence is limited. The current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program for patients with SSD and predominant (spinal) pain. METHOD: The healthcare program consisted of two active treatment phases: main 20-week program and a 12-month relapse prevention program. Participants were 4453 patients diagnosed with SSD. The primary outcome was health-related quality of life (HRQoL) assessed using the RAND-36 (i.e., mental/physical component summary) and secondary outcomes included physical and psychological symptoms assessed using the Brief Symptom Inventory (BSI) and RAND-36 subscales. Mixed linear models were used to examine the effects of the multimodal healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of relapse prevention program (T3). RESULTS: Significant improvements were found from T0 to T2 for all primary variables (i.e., mental/physical component summary) and secondary variables (i.e., BSI/RAND-36 subscales), which were maintained until the end of the relapse prevention program (T3). CONCLUSION: An interdisciplinary multimodal integrative treatment for SSD is effective for improving HRQoL and reducing physical and psychological symptoms.

The Effect of Praying on Endogenous Pain Modulation and Pain Intensity in Healthy Religious Individuals in Lebanon: A Randomized Controlled Trial.

Prayer is considered to be the most common therapy used in alternative medicine. This study aimed to explore the effect of prayers on endogenous pain modulation, pain intensity, and sensitivity in healthy religious participants. A total of 208 healthy religious participants were enrolled in this study and randomly distributed into two groups, a prayer group (n = 156) and a poem reading or control group (n = 52). Participants from the prayer group were then selectively allocated using the prayer function scale to either an active prayer group (n = 94) receiving an active type of praying or to a passive prayer group (n = 62) receiving a passive type of praying. Pain assessments were performed before and following the interventions and included pressure pain threshold assessment (PPT), conditioned pain modulation (CPM), and a numerical pain rating scale. A significant group-by-time interaction for PPT (p = 0.014) indicated post-intervention increases in PPT in the prayer group but not in the poem reading control group. Participants experienced a decrease in CPM efficacy (p = 0.030) and a reduction in their NPRS (p < 0.001) following the interventions, independent of their group allocation. The results showed that prayer, irrespective of the type, can positively affect pain sensitivity and intensity, but does not influence endogenous pain inhibition during hot water immersion. Future research should focus on understanding the mechanism behind "prayer-induced analgesia."

The Relationship Between Pain-Related Psychological Factors and Maximal Physical Performance in Low Back Pain: A Systematic Review and Meta-Analysis.

Theoretical frameworks explain how pain-related psychological factors may influence the physical performance. In this systematic review and meta-analysis, we evaluated the evidence regarding the relationship between the pain-related psychological factors and the maximal physical performance in patients with low back pain (LBP). Pubmed, Embase, CINAHL and Web of Science databases were searched from inception to May 2022. Cross-sectional or longitudinal studies reporting cross-sectional measures of association between at least one pain-related psychological factor and a quantitatively measured outcome of maximal physical performance in patients with LBP were eligible for inclusion. Thirty-eight studies (n = 2,490; 27 cross-sectional studies, n = 1,647 (66%); 11 longitudinal studies, n = 843 (34%)) were included, with 92% of participants (n = 2,284) having chronic LBP. Results showed that pain-related fear, pain catastrophizing, and anticipated pain were consistently and negatively associated with the maximal physical performance in chronic LBP, whereas pain-self efficacy showed positive correlations. Overall, magnitudes of absolute pooled r-values were small (r ≤ 0.25), except for anticipated pain, which was moderately associated with maximal physical performance (r = -0.34 to -0.37). Subanalyses and sensitivity analyses yielded similar pooled correlation coefficients. Certainty of evidence using the GRADE recommendations was very low to moderate for pain-related fear, and very low to low for the other pain-related psychological factors. Prospero registration: CRD42021227486. PERSPECTIVE: Overall, small pooled correlation coefficients were shown between pain-related psychological factors and maximal physical performance in chronic LBP. Certainty of evidence was very low to low for all pain-related psychological factors other than pain-related fear. Future studies taking into account limitations of the current literature may therefore change these conclusions.

Systemic Cytokine Level Differences in Patients with Chronic Musculoskeletal Spinal Pain Compared to Healthy Controls and Its Association with Pain Severity: A Systematic Review.

OBJECTIVE: Although there has been increasing interest in the role of systemic cytokines in chronic spinal pain (CSP), the evidence on their potential contribution is still unclear. Therefore, the current study systematically reviewed the evidence on systemic cytokine level differences between people with CSP compared to healthy controls (HCs) and the potential associations with pain severity. METHODS: An electronic search was conducted on PubMed, Web of Science and Embase. All included studies were classified as observational studies, exploring the comparison between a CSP group and a HC group, and the association between systemic cytokine levels and pain severity. RESULTS: Nine articles were included with a total sample of 400 CSP patients suffering from chronic whiplash associated disorder (CWAD) or chronic low back pain (CLBP). In CLBP, moderate evidence was found for elevated tumor necrosis factor (TNF) α, interleukin (IL) 6, IL-1 receptor antagonist (IL-1RA), and soluble TNF receptor (sTNF-R) type 2, for normal interferon (IFN) γ and IL-2 levels, and for reduced IL-10 levels. No association was found between pain severity and these cytokines in CLBP. In CWAD, moderate evidence was found for elevated CRP and evidence for changes in TNF-α was inconclusive. Evidence for the association between pain severity and CRP was limited, and there is probably no association between pain severity and TNF-α with limited evidence in CWAD. CONCLUSIONS: Moderate evidence indicates the presence of systemic inflammation in CSP. Evidence regarding the association between pain severity and systemic cytokines is inconclusive and limited.

Exploring pain mechanisms in hypermobile Ehlers-Danlos syndrome: A case-control study.

BACKGROUND: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder, associated with joint hypermobility and prominent chronic pain. Because experimental pain testing in hEDS is scarce, the underlying mechanisms are still poorly understood. OBJECTIVE: The present study assesses endogenous pain facilitation and pain inhibition in hEDS, using a protocol for temporal summation of pain (TSP), conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH). METHODS: Twenty women with hEDS and 20 age-matched healthy controls participated. After evaluating thermal and mechanical pain thresholds (PPT), TSP was assessed using 10 repetitive painful pressure stimuli. CPM was provoked using pressure as the test stimulus and hand immersion in hot water (46°) as the conditioning stimulus. EIH was assessed after a submaximal cycling protocol. RESULTS: The hEDS group demonstrated reduced PPTs and showed significantly more TSP after repeated painful stimuli than the control group. In comparison to the healthy control group, the hEDS group demonstrated significantly less EIH at the quadriceps test location. At the trapezius, EIH did not significantly differ between groups. No significant differences were found between the hEDS group and control group in the CPM response. CONCLUSION: The results demonstrate increased TSP in hEDS, suggesting increased central pain facilitation. EIH should be studied more extensively but may be disturbed when evaluated in the muscles that are activated during exercise. The CPM results are inconclusive and require more research. SIGNIFICANCE: Studies regarding the mechanisms that underlie pain in hEDS are scarce, although it is the most prevalent and disabling symptom in this patient population. This study demonstrates increased temporal summation in hEDS and suggests that exercise-induced hypoalgesia may be reduced. Because exercise is a cornerstone in the multidisciplinary treatment of heritable connective tissue disorders, gaining knowledge in this field is important. Pressure stimuli were used to facilitate the international usability of the protocols, allowing for future data acquisition in large cohorts.

Modulation of the nociceptive flexion reflex by conservative therapy in patients and healthy people: a systematic review and meta-analysis.

ABSTRACT: The nociceptive flexion reflex (NFR) is a spinally mediated withdrawal response and is used as an electrophysiological marker of descending modulation of spinal nociception. Chemical and pharmacological modulation of nociceptive neurotransmission at the spinal level has been evidenced by direct effects of neurotransmitters and pharmacological agents on the NFR. Largely unexplored are, however, the effects of nonpharmacological noninvasive conservative interventions on the NFR. Therefore, a systematic review and meta-analysis was performed and reported following the PRISMA guidelines to determine whether and to what extent spinal nociception measured through the assessment of the NFR is modulated by conservative therapy in patients and healthy individuals. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using the predefined inclusion criteria. Risk of bias was investigated according to Version 2 of the Cochrane risk-of-bias assessment tool for randomized trials. The evidence synthesis for this review was conducted in accordance with the Grading of Recommendations Assessment, Development and Evaluation. Thirty-six articles were included. Meta-analyses provided low-quality evidence showing that conservative therapy decreases NFR area and NFR magnitude and moderate-quality evidence for increases in NFR latency. This suggests that conservative interventions can exert immediate central effects by activating descending inhibitory pathways to reduce spinal nociception. Such interventions may help prevent and treat chronic pain characterized by enhanced spinal nociception. Furthermore, given the responsiveness of the NFR to conservative interventions, the NFR assessment seems to be an appropriate tool in empirical evaluations of treatment strategies.PROSPERO registration number: CRD42020164495.

Religious Beliefs and Attitudes in Relation to Pain, Pain-Related Beliefs, Function, and Coping in Chronic Musculoskeletal Pain: A Systematic Review.

BACKGROUND: The biopsychosocial-spiritual model recognizes the impact of religious factors in modulating the experience of pain. Religious beliefs are factors that can influence perceptions, emotions, and behavior, all of which have important implications on health, pain experience, and treatment outcomes. OBJECTIVES: The aim of the present study was to identify if and how religious beliefs and attitudes can influence pain intensity, pain interference, pain-related beliefs and cognitions, emotions, and coping among patients with chronic musculoskeletal pain. STUDY DESIGN: Systematic review. METHODS: This systematic review was conducted and reported, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). An electronic search was conducted in 4 online databases (PubMed, Embase, Web of science, and PsychArticles) and complemented with a hand search (PROSPERO registry: CRD42020161289). Two reviewers independently performed eligibility screening, risk of bias assessment, and data extraction. The risk of bias of the included studies was assessed using the Newcastle Ottawa Scale. RESULTS: Nine cross-sectional studies and one case-control study were included in the review. The methodological quality of the included studies ranged from low to high. The results gathered regarding the association between religiosity and pain intensity, disability, or pain interference were found to be conflicting. Limited evidence suggests that religiosity is positively associated with worse pain-related beliefs and cognitions, worse pain-related emotion, and better pain acceptance. There is insufficient data available to support the claim that religiosity is negatively associated with physical functioning and pain-related self-efficacy in people with chronic musculoskeletal pain. LIMITATIONS: The number of included studies was small, with a low level of evidence, and a possible risk of bias. CONCLUSION: This systematic review shows low evidence and conflicting results for the presence of associations between religiosity and different pain domains such as pain intensity, disability, and pain-related cognitions or emotions in people with chronic musculoskeletal pain.

Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.

Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients.

BACKGROUND: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. METHODS: Chronic fatigue syndrome (CFS) patients were assessed using Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO2peak, VO2submax and heart rate (HR) were assessed using cardiopulmonary exercise testing. Mfn1 and Mfn2 levels in plasma were assessed. A Task Force Monitor was used to assess ANS functioning in supine rest and in response to the Head-Up Tilt Test (HUTT). RESULTS: Thirty-four patients completed 16 weeks of the IAP. The CFQ, FSS and FIS scores decreased significantly along with a significant increase in Mfn1 and Mfn2 levels (p = 0.002 and p = 0.00005, respectively). The relationships between VO2 peak and Mfn1 increase in response to IAP (p = 0.03) and between VO2 at anaerobic threshold and ANS response to the HUTT (p = 0.03) were noted. CONCLUSIONS: It is concluded that IAP reduces fatigue and improves functional performance along with changes in autonomic and mitochondrial function. However, caution must be applied as exercise was not well tolerated by 51% of patients.