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Kristian Johnsen,1 Patrick J Owen,1 Scott D Tagliaferri,1 Jessica Van Oosterwijck,2– 4 Bernadette M Fitzgibbon,5 Jon J Ford,6,7 Daniel L Belavy,1,8 Clint T Miller1 1Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia; 2Spine, Head and Pain Research Unit Ghent, Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; 3Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; 4Research Foundation – Flanders (FWO), Brussels, Belgium; 5School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; 6Advance HealthCare, Boronia, VIC, Australia; 7Low Back Research Team, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC, Australia; 8Department of Applied Health Sciences, Division of Physiotherapy, Hochschule für Gesundheit, Bochum, GermanyCorrespondence: Clint T Miller, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC, 3125, Australia, Tel +61 3 9244 6605, Email c.miller@deakin.edu.auPurpose: 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.Keywords: aerobic exercise, acute exercise, pain pressure threshold, perceived social support, kinesiophobia

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Clauwaert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: DLB, ST, MT, LS, SeS, HJW, MA, GT, KE, BF, JVO, CTM, PJO, SB, RD, SK declare no conflicts of interest. BB: declares no conflicts of interest relevant to the current work, but has previously received research support, consultancy fees and/or honoraria from AbbVie, Amgen, Biogen, GE/Lunar, Janssen, Galapagos, Gilead, Medimaps, MSD, Sanofi Genzyme, Theramex, UCB. TS: declares prior consulting fees from Johnson & Johnson, Amgen, Kaia Health Software, SpineArt, Implantcast and speaking and travel arrangements from Johnson & Johnson, ICOTEC, Nuvasive, Ulrichmedical, Silony, Amgen, Kaia Health Software. EE-K has received fees from painCert GmbH, Casquar GmbH and Omega Pharma GmbH, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Belavy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. Springer Nature Limited.)

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., Competing Interests: JW, NG, GH, MP, MG, and JJ are employed by Intergrin Academy. Intergrin Academy evaluates and improves specialized secondary care formats such as offered at ‘PHI’. Intergrin Academy and ‘PHI’ are part of the same overarching organization: Integrative Interventions Group. In addition, JW was a former employee of ‘Het Rughuis’, a mental healthcare facility also part of Integrative Interventions Group., (Copyright © 2023 Wijnen, Gordon, van 't Hullenaar, Pont, Geijselaers, Van Oosterwijck and de Jong.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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.

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.

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). VO 2 peak, VO 2 submax 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 VO 2 peak and Mfn1 increase in response to IAP ( p = 0.03) and between VO 2 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.

Background: Pain can be influenced by several factors, including stress. Stress can have various reactions on pain. These reactions are influenced by several internal factors such as gender, age, and experience with stress or pain., Objectives: To determine the effect of acute stress on mechanical hyperalgesia (with pressure pain thresholds [PPT]), endogenous pain facilitation (measured by temporal summation [TS]), and inhibition (measured by conditioned pain modulation [CPM]) in healthy people and to determine which factors are responsible for this stress result., Study Design: Pre-posttest design., Setting: Healthy volunteers from Belgium., Methods: One hundred and one healthy pain-free patients underwent a modified Trier Social Stress Test. Prior and following the stress manipulation, PPT, TS, and CPM efficacy were determined in the mm. trapezius and quadriceps and overall. Furthermore, possible explanatory factors, such as fear of pain, pain catastrophizing, pain hypervigilance, and daily activity levels, were assessed using questionnaires., Results: We found a significant stress result on widespread pain sensitivity, with an increase of PPT (P < 0.001), unchanged TS (P > 0.05), and a decrease in CPM efficacy (P < 0.001). Factors associated with the stress result were age, previous surgery, attentional focus on the conditioning stimulus during CPM, fear of pain, and daily activity levels., Limitations: The efficacy of the stress manipulation was not examined, and the lack of a control group prevented to examine a real stress-effect. Furthermore, no physiologic parameters were measured as possibly influencing internal factors for the stress-result., Conclusions: The increase in PPT was not a clinically significant change, whereas the decrease in CPM was meaningful. None of the factors predicted the stress result in all experimental pain measurements, and the predictions that were observed only explained a small proportion of the observed effects.

This systematic review analyzed available literature on functional brain alterations in low back pain (LBP) measured with electroencephalography (EEG), as until now evidence thereof was unclear. Four electronic databases were systematically searched the 10th of March 2018, resulting in 12 included studies. Studies showed a risk of bias of 37.5 to 75% using the Newcastle-Ottawa Scale for case-control studies. Limited evidence reported higher amplitudes of balance-related potentials and early components of somatosensory evoked potentials (SEP) to noxious stimuli, and altered feedback-related negativity and P300 potentials during decision-making in chronic LBP (CLBP). These findings suggest postural strategies requiring a higher cortical attention-demand, increased sensory-discriminative processing of noxious input, and altered decision-making in CLBP. However, further research is warranted as these inferences were based on single studies. Moderate evidence for unaltered amplitude of late-phase SEPs to noxious stimuli and auditory evoked potentials in LBP implies that the affective-emotional processing of stimuli might be unaffected in LBP. Furthermore, moderate evidence indicated disturbed habituation of somatosensory stimuli in LBP. Most studies examined nonspecific or mixed CLBP populations, hence EEG-quantified brain activity in (sub)acute or recurrent LBP still needs to be explored. PERSPECTIVE: This review presents an overview of the current understanding of the functional LBP brain measured with EEG. The limited evidence in current research suggests altered cortical function regarding balance control, somatosensory processing, and decision making in LBP, and highlights opportunities for future EEG-research., (Copyright © 2019. Published by Elsevier Inc.)

Patients with chronic obstructive pulmonary disease (COPD) show several extrapulmonary abnormalities such as impairment in the autonomic function (AF). Similarly, the use of respiratory training techniques such as controlled breathing techniques, noninvasive mechanical ventilation (NIMV), and oxygen supplementation for AF modulation in patients with COPD is popular in existing literature. However, the evidence to support their use is nonexistent. A systematic search of studies reporting on the effect of controlled breathing techniques, NIMV, and/or oxygen supplementation techniques on AF outcome parameters was conducted in three online databases: PubMed, Embase, and Web of Science. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, relevant studies were retained and qualitatively analyzed for evidence synthesis. The methodological quality in these studies was evaluated using the evidence based guideline development (EBRO) checklists per designs provided by the Dutch Cochrane Centre. Eighteen studies met the inclusion criteria of the review and were included and discussed. The evidence synthesis revealed that a strong and moderate level evidence supported oxygen supplementation and slow breathing techniques, respectively, in significantly enhancing the baroreceptor sensitivity (BRS) values in patients with COPD. The effect of the examined techniques on the heart rate variability and muscle sympathetic nerve activity was of a limited or inconsistent evidence. The findings from this review suggest that oxygen supplementation and controlled breathing techniques have profound positive influence on the BRS in patients with COPD. However, it is not fully clear whether these influence translates to any therapeutic benefit on the general AF of patients with COPD in the long term.

Background: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy., Objective: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM., Study Design: A systematic review of research studies that investigated the application or mechanisms of OA., Setting: The present study took place at Ghent University and the University of Antwerp., Methods: This systematic review follows the PRISMA guidelines. The electronic databases Pubmed and Web of Science were searched in January 2015. Full text clinical reports addressing OA were included. The checklists for randomized controlled trials, case-control studies, and cohort-studies provided by the Dutch Institute for Healthcare Improvement and the Dutch Cochrane Centre were used to assess methodological quality. The articles received a level of evidence A1, A2, B, C, or D, based on study design and risk of bias. These levels were used to determine the strength of conclusion (level 1 to 4)., Results: Seventeen articles met the inclusion criteria. Sixteen studies used quantitative sensory testing to provoke OA; however, differences in protocols are present. OA can function as a non-opioid mediated assessment tool for endogenous pain inhibition, and activates brain regions such as periaqueductal gray (PAG), dorsolateral prefontral cortex, insula, medulla, pons and cerebellum, indicating strong brain derived pain modulation. The primary somatosensory cortex is, conversely, less activated during OA. OA is decreased in neuropathic patients. Nonetheless, evidence for the influence of individual factors on OA is limited. OA and CPM seem to rely on different mechanisms., Limitations: Search strategy was taken wide, wherefore a large variety of research perspectives were included., Conclusions: This systematic review displays OA as a temporal filtering mechanisms that is more brain-derived compared to the spatial assessment method CPM. There is strong evidence for reduced OA in neuropathic patients, however, evidence regarding OA in (sub)acute and central sensitization patients, and the influence of personal factors on OA is currently scarce and needs further investigation.

Background: Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM., Objectives: The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals., Study Design: A randomized crossover design was employed., Setting: The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp., Methods: Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched., Results: A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001)., Limitations: The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies., Conclusions: A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons. However, endogenous pain inhibition, assessed using a CPM paradigm, worsened in chronic WAD and FM patients, as well as in healthy people following both interventions.

In people with a history of low back pain (LBP), structural and functional alterations have been observed at several peripheral and central levels of the sensorimotor pathway. These existing alterations might interact with the way the sensorimotor system responds to pain. We examined this assumption by evaluating the lumbar motor responses to experimental nociceptive input of 15 participants during remission of unilateral recurrent LBP. Quantitative T2 images (muscle functional MRI) were taken bilaterally of multifidus, erector spinae, and psoas at several segmental levels (L3 upper and L4 upper and lower endplate) and during several conditions: 1) at rest, 2) upon trunk-extension exercise without pain, and 3) upon trunk-extension exercise with experimental induced pain at the clinical pain-side (1.5-ml intramuscular hypertonic saline injections in erector spinae). Following experimental pain induction, muscle activity levels similarly reduced for all three muscles, on both painful and nonpainful sides, and at multiple segmental levels (P = 0.038). Pain intensity and localization from experimental LBP were similar as during recalled clinical LBP episodes. In conclusion, unilateral and unisegmental experimental LBP exerts a generalized and widespread decrease in lumbar muscle activity during remission of recurrent LBP. This muscle response is consistent with previous observed patterns in healthy people subjected to the same experimental pain paradigm. It is striking that similar inhibitory patterns in response to pain could be observed, despite the presence of preexisting alterations in the lumbar musculature during remission of recurrent LBP. These results suggest that motor output can modify along the course of recurrent LBP., (Copyright © 2016 the American Physiological Society.)

Background: The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists., Objectives: Designing the first set of classification criteria for the classification of central sensitization pain., Methods: A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain., Results: It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory)., Limitations: Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies., Conclusion: Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain.

Chronic spinal pain (CSP) is a severely disabling disorder, including nontraumatic chronic low back and neck pain, failed back surgery, and chronic whiplash-associated disorders. Much of the current therapy is focused on input mechanisms (treating peripheral elements such as muscles and joints) and output mechanisms (addressing motor control), while there is less attention to processing (central) mechanisms. In addition to the compelling evidence for impaired motor control of spinal muscles in patients with CSP, there is increasing evidence that central mechanisms (ie, hyperexcitability of the central nervous system and brain abnormalities) play a role in CSP. Hence, treatments for CSP should address not only peripheral dysfunctions but also the brain. Therefore, a modern neuroscience approach, comprising therapeutic pain neuroscience education followed by cognition-targeted motor control training, is proposed. This perspective article explains why and how such an approach to CSP can be applied in physical therapist practice.

An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise. The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects. A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise. The included articles were evaluated on their methodological quality. Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells' gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines. Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.

Background: Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation)., Objectives: Reviewing the available evidence addressing the effects of exercise on central pain modulation in patients with chronic pain., Methods: Narrative review., Results: Exercise activates endogenous analgesia in healthy individuals. The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain. Exercise triggers the release of beta-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively. The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms. However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain. Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients. In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia. However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations., Limitations: The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy., Conclusions: A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares. The paper discusses the translation of these findings to rehabilitation practice together with future research avenues.

Unlabelled: A controlled experimental study was performed to examine the efficacy of the endogenous pain inhibitory systems and whether this (mal)functioning is associated with symptom increases following exercise in patients with chronic whiplash-associated disorders (WAD). In addition, 2 types of exercise were compared. Twenty-two women with chronic WAD and 22 healthy controls performed a submaximal and a self-paced, physiologically limited exercise test on a cycle ergometer with cardiorespiratory monitoring on 2 separate occasions. Pain pressure thresholds (PPT), health status, and activity levels were assessed in response to the 2 exercise bouts. In chronic WAD, PPT decreased following submaximal exercise, whereas they increased in healthy subjects. The same effect was established in response to the self-paced, physiologically limited exercise, with exception of the PPT at the calf which increased. A worsening of the chronic WAD symptom complex was reported post-exercise. Fewer symptoms were reported in response to the self-paced, physiologically limited exercise. These observations suggest abnormal central pain processing during exercise in patients with chronic WAD. Submaximal exercise triggers post-exertional malaise, while a self-paced and physiologically limited exercise will trigger less severe symptoms, and therefore seems more appropriate for chronic WAD patients., Perspective: The results from this exercise study suggest impaired endogenous pain inhibition during exercise in people with chronic WAD. This finding highlights the fact that one should be cautious when evaluating and recommending exercise in people with chronic WAD, and that the use of more individual, targeted exercise therapies is recommended., (Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Chronic whiplash is a debilitating condition characterized by increased sensitivity to painful stimuli, maladaptive illness beliefs, inappropriate attitudes, and movement dysfunctions. Previous work in people with chronic low back pain and chronic fatigue syndrome indicates that pain neurophysiology education is able to improve illness beliefs and attitudes as well as movement performance. This single-case study (A-B-C design) with six patients with chronic whiplash associated disorders (WAD) was aimed at examining whether education about the neurophysiology of pain is accompanied by changes in symptoms, daily functioning, pain beliefs, and behavior. Periods A and C represented assessment periods, while period B consisted of the intervention (pain neurophysiology education). Results showed a significant decrease in kinesiophobia (Tampa Scale for Kinesiophobia), the passive coping strategy of resting (Pain Coping Inventory), self-rated disability (Neck Disability Index), and photophobia (WAD Symptom List). At the same time, significantly increased pain pressure thresholds and improved pain-free movement performance (visual analog scale on Neck Extension Test and Brachial Plexus Provocation Test) were established. Although the current results need to be verified in a randomized, controlled trial, they suggest that education about the physiology of pain is able to increase pain thresholds and improve pain behavior and pain-free movement performance in patients with chronic WAD.