Search

Purpose: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls., Methods: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale., Findings: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001)., Implications: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and aims The interaction between the immune system and pain has been thoroughly explored in the recent decades. The release of inflammatory mediators from immune cells has the capability of activating neurons and glial cells, in turn sensitizing the nervous system. Both immune system alterations and pain modulation dysfunctions have been shown in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following exercise. However, no studies tried to explore whether these two phenomena are linked and can explain exercise-induced symptoms worsening in people with ME/CFS. We hypothesized that exercise-induced changes in descending pain modulation is associated to changes in immune system functions. We used complement system product C4a and elastase activity as indicators of immune system activity. Methods The study design was a secondary analysis of controlled experimental studies. Twenty-two patients with ME/CFS and 22 healthy sedentary controls were enrolled. In experiment 1, subjects performed an aerobic submaximal exercise test; in experiment 2 they underwent a self-paced exercise test. One week of rest period were set between the two exercise tests. Before and after each experiment, subjects underwent clinical assessment, pain thresholds (PPTs) measurement, and blood sampling. Immune system function was assessed measuring complement system C4a products and elastase activity. Results Changes in elastase activity were not associated to changes in PPTs. Associations were observed in the ME/CFS group between changes in PPTs and C4a products, following both types of exercise. After submaximal exercise, the change in C4a products was associated with the change in PPT at the thumb in patients (r=0.669, p=0.001). Similarly, after self-paced exercise the change in C4a products was associated witht the change in PPT at the calf in patients (r=0.429, p=0.047). No such correlations were found in healthy controls. Regression analysis showed that C4a changes after the submaximal exercise significantly predicted the change in PPTs (R2=0.236; p=0.02). Conclusions Moderate associations between exercise-induced changes in PPTs and immune system activity were found only in ME/CFS. The change in the complement system following submaximal exercise might be able to explain part of the change in patient's pain thresholds, providing evidence for a potential link between immune system alteration and dysfunctional endogenous pain modulation. These results have to be taken with caution, as only one out of three measures of PPTs was found associated with C4a changes. We cannot reject the hypothesis that C4a might therefore be a confounding factor, and changes during exercise might be mediated by other mechanism. Implications Immune system changes following exercise might contribute to exercise-induced symptoms worsening in patients with ME/CFS. However, the role of the complement system is questionable.

Many patients with chronic fatigue syndrome(CFS) and/or fibromyalgia(FM) have little understanding of their condition, leading to maladaptive pain cognitions and coping strategies. These should be tackled during therapy, for instance by pain neurophysiology education (PNE). Although positive effects of PNE are well-established, it remains unclear why some patients benefit more than others. This paper aims at exploring characteristics of patients responding poor to PNE to further improve its effectiveness. Data from two RCT's were pooled to search for baseline predictors. Subjects (n = 39) suffering from CFS/FM, as defined by the American College of Rheumatology, underwent PNE treatment. The Pain Catastrophizing Scale (PCS); Pain Coping Inventory (PCI); and Tampa Scale of Kinesiophobia (TSK) were defined as outcome measures. There was a significant negative relationship between baseline TSK and the change in both PCS total score (r = -0.584; p < 0.001) and PCS rumination (r = -0.346; p < 0.05). There was a significant negative relationship between the change in PCS total score and baseline PCI worrying (r = -0.795; p < 0.001) and retreating (r = -0.356; p < 0.05). FM/CFS patients who tend to worry allot about their pain and with high levels of kinesiophobia are likely to experience less reductions in catastrophizing following PNE. It seems that PNE alone is insufficient to reduce catastrophic thinking regarding pain, and supplementary treatment is needed.

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.

Severe exacerbation of symptoms following physical activity is characteristic for chronic-fatigue syndrome (CFS) and fibromyalgia (FM). These exacerbations make it understandable for people with CFS and FM to develop fear of performing body movement or physical activity and consequently avoidance behaviour toward physical activity. The aims of this article were to review what measures are available for measuring fear of movement and avoidance behaviour, the prevalence fear of movement and avoidance behaviour toward physical activity and the therapeutic options with fear of movement and avoidance behaviour toward physical activity in patients with CFS and FM. The review revealed that fear of movement and avoidance behaviour toward physical activity is highly prevalent in both the CFS and FM population, and it is related to various clinical characteristics of CFS and FM, including symptom severity and self-reported quality of life and disability. It appears to be crucial for treatment (success) to identify CFS and FM patients displaying fear of movement and avoidance behaviour toward physical activity. Individually tailored cognitive behavioural therapy plus exercise training, depending on the patient's classification as avoiding or persisting, appears to be the most promising strategy for treating fear of movement and avoidance behaviour toward physical activity in patients with CFS and FM.

Background: Central sensitisation entails several top-down and bottom-up mechanisms, all contributing to the hyperresponsiveness of the central nervous system to a variety of inputs. In the late nineties, it was first hypothesised that chronic fatigue syndrome (CFS) is characterised by hypersensitivity of the central nervous system (i.e. central sensitisation). Since then, several studies have examined central sensitisation in patients with CFS. This study provides an overview of such studies., Materials and Methods: Narrative review., Results: Various studies showed generalised hyperalgesia in CFS for a variety of sensory stimuli, including electrical stimulation, mechanical pressure, heat and histamine. Various tissues are affected by generalised hyperalgesia: the skin, muscle tissue and the lungs. Generalised hyperalgesia in CFS is augmented, rather than decreased, following various types of stressors like exercise and noxious heat pain. Endogenous inhibition is not activated in response to exercise and activation of diffuse noxious inhibitory controls following noxious heat application to the skin is delayed., Conclusions: The observation of central sensitisation in CFS is in line with our current understanding of CFS. The presence of central sensitisation in CFS corroborates with the presence of several psychological influences on the illness, the presence of infectious agents and immune dysfunctions and the dysfunctional hypothalamus-pituitary-adrenal axis as seen in these severely debilitated patients., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.

Objectives: To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise., Design: A controlled experimental study., Setting and Subjects: Twenty-two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel., Interventions: All subjects performed a submaximal exercise test and a self-paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects' activity levels were assessed using accelerometry., Results: In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post-exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r = 0.454; P = 0.034)., Conclusions: These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self-paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.

Objective: To examine whether pain physiology education was capable of changing pain cognitions and pain thresholds in patients with chronic fatigue syndrome (CFS) and chronic widespread pain., Design: Double-blind randomized controlled trial., Setting: Specialized chronic fatigue clinic in university hospital., Participants: A random sample of patients (N=48) with CFS patients (8 men, 40 women) experiencing chronic pain, randomly allocated to the control group (n=24) or experimental group (n=24). Two women in the experimental group did not complete the study because of practical issues (lack of time and restricted mobility)., Interventions: One individual pain physiology education session (experimental) or 1 pacing and self-management education session (control)., Main Outcome Measures: Algometry, the Neurophysiology of Pain Test, and questionnaires evaluating pain cognitions-the Pain Coping Inventory, the Pain Catastrophizing Scale, and the Tampa Scale for Kinesiophobia-version CFS-were completed immediately before and immediately after the intervention., Results: After the intervention, the experimental group demonstrated a significantly better understanding of the neurophysiology of pain (P<.001) and a reduction of the Pain Catastrophizing Scale subscale "ruminating" (P=.009) compared with controls. For these variables, moderate to large Cohen d effect sizes were revealed (.79-2.53)., Conclusions: A 30-minute educational session on pain physiology imparts a better understanding of pain and brings about less rumination in the short term. Pain physiology education can be an important therapeutic modality in the approach of patients with CFS and chronic pain, given the clinical relevance of inappropriate pain cognitions.

Objectives: Too vigorous exercise or activity increase frequently triggers postexertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a primary characteristic evident in up to 95% of people with ME/CFS. The present study aimed at examining whether two different types of exercise results in changes in health status, circulating elastase activity, interleukin (IL)-1beta and complement C4a levels., Design: Comparative experimental design., Setting: University., Subjects: Twenty-two women with ME/CFS and 22 healthy sedentary controls, Interventions: participants were subjected to a submaximal exercise (day 8) and a self-paced, physiologically limited exercise (day 16). Each bout of exercise was preceded and followed by blood sampling, actigraphy and assessment of their health status., Results: Both submaximal exercise and self-paced, physiologically limited exercise resulted in postexertional malaise in people with ME/CFS. However, neither exercise bout altered elastase activity, IL-1beta or complement C4a split product levels in people with ME/CFS or healthy sedentary control subjects (P > 0.05). Postexercise complement C4a level was identified as a clinically important biomarker for postexertional malaise in people with ME/CFS., Conclusions: Submaximal exercise as well as self-paced, physiologically limited exercise triggers postexertional malaise in people with ME/CFS, but neither types of exercise alter acute circulating levels of IL-1beta, complement C4a split product or elastase activity. Further studying of immune alterations in relation to postexertional malaise in people with ME/CFS using multiple measurement points postexercise is required.