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Even in healthy populations, conditioned pain modulation (CPM) magnitude varies. This may be accounted for by (non-)modifiable factors, including physical activity (PA). Yet, little research has thoroughly examined PA and its relation with CPM magnitude in a representative sample. Therefore, the present study investigated the predictive effect of PA on CPM magnitude in 105 healthy adults. PA was assessed during 7 consecutive days by self-report using the International Physical Activity Questionnaire and by monitor-based accelerometry. CPM was examined using a heterotopic noxious-conditioning stimulation protocol during which the effect of a hot water-conditioning stimulus on pressure pain thresholds was evaluated. Comparative, correlation, and hierarchical linear regression analyses were performed. Report-based walking predicts 4.8% of variance in pain-modulatory capacity, moderate PA predicts 10.2% of variance in pain-modulatory capacity, and report-based time spent on total PA predicts 7.0% of variance in pain-modulatory capacity. More metabolic equivalent-minutes/week spent on total PA, including walking and moderate PA, is associated with greater pain-modulatory capacity. The findings of this study add to the limited evidence on the predictive effect of PA on CPM. It urges to consider PA a confounding factor when examining CPM. The current study provides evidence that a physically active lifestyle benefits endogenous pain modulation in healthy adults. Given its potential, walking and moderate-intensity PA might be achievable treatment strategies for pain patients known to have impaired CPM. PERSPECTIVE: The results of this article show that a physically active lifestyle, including larger amounts of walking and moderate activity, predicts greater pain-modulatory capacity. TRIAL REGISTRATION: This study has not been preregistered., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in an appropriate withdrawal response. The NFR is considered to be an objective physiological correlate of spinal nociception. Previous research has already demonstrated that physical activity (PA) can influence pain assessments. To date, no studies have directly examined the relationship between PA and spinal nociception. Hence, this study aimed to investigate whether the NFR threshold can be predicted by report-based and monitor-based measures of PA in healthy adults., Methods: PA and the NFR threshold of 58 healthy adults were assessed. PA was evaluated by self-report using the International Physical Activity Questionnaire and by monitor-based accelerometry data. The NFR threshold was elicited through transcutaneous electrical stimulation of the sural nerve and quantified by the biceps femoris muscle electromyogram. Hierarchical linear regression analyses were performed to determine the relationship between PA and the NFR, while controlling for confounders., Results: Monitor-based measured step count and activities of moderate- to vigorous-intensity predicted the NFR threshold accounting for 23.0% (p = .047) to 37.1% (p = .002) of the variance. Larger amounts of step counts and higher participation in moderate- to vigorous-intensity activities predicted higher NFR thresholds. Monitor-based activities of sedentary intensity predicted the NFR threshold accounting for 35.8% (p = .014) to 35.9% (p = .014) of the variance. Spending more time per day on activities of sedentary intensity predicted lower NFR thresholds., Conclusions: The study provides preliminary evidence indicating that a physically active lifestyle may reduce spinal nociception in healthy adults, while a sedentary lifestyle enhances spinal nociception., Significance: The present study provides preliminary evidence that the influencing effects of physical activity on pain are the result of a strong descending control and do not purely rely on supraspinal mechanisms. These study results highlight the importance of considering physical activity levels when evaluating nociceptive processing, given the prognostic value of physical activity in spinal nociception. Furthermore, this study encourages future research to examine the effects of moderate- to vigorous-intensity exercise programmes on spinal nociception in chronic pain populations., (© 2020 European Pain Federation - EFIC®.)

BELAVY, D. L., J. Van Oosterwijck, M. Clarkson, E. Dhondt, N. L. Mundell, C. Miller and P. J. Owen. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2020. Exercise training is capable of reducing pain in chronic pain syndromes, yet its mechanisms are less well established. One mechanism may be via the impact of exercise on increasing a person's pain threshold. Here we show, via meta-analysis of fifteen exercise training studies in pain syndromes that exercise training leads to increased pressure pain thresholds (low to moderate quality evidence). We also find low to moderate quality evidence exists that exercise training was more effective than non-exercise interventions, such as pain education, massage and stress management for improving pain sensitivity. Further, the effect of exercise was greater locally at the site of pain and less so at remote regions. These finding suggest that adaptations in central inhibition occur over time with exercise training and, more widely, add to the mechanistic understanding of how effective interventions can improve pain in chronic pain syndromes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Conditioned pain modulation (CPM) methods are experimental procedures to assess presumed descending nociceptive modulatory pathways. Various CPM-methods are currently used, making the comparison of results difficult. The aim of this study was to compare five conditioning stimuli and to evaluate the influencing effects of personal factors on CPM-efficacy., Methods: 101 healthy pain-free adults (50 males, 51 females) participated in this cross-sectional study with repeated measures design. The CPM-method consisted of hot water immersion (46°C, HWI), cold pressor test (12°C, CPT), cold pack application, and single and double ischemic occlusion as conditioning stimuli in randomized order. Pressure pain threshold was used as test stimulus at the mm. trapezius and quadriceps for all CPM-protocols., Results: All CPM-protocols resulted in effective CPM, although cold pack application revealed smaller CPM-magnitudes compared to all other methods at both muscles, except single ischemic occlusion at the m. quadriceps. A smaller CPM-effect at the m. trapezius was shown when CPM was provoked by single ischemic occlusion compared to the CPT. Chronic stress, gender, attentional focus, age, physical activity and perceived pain are all influencing factors, in various conditioning stimuli at the mm. trapezius and quadriceps., Conclusions: CPT and HWI seem to be the most appropriate conditioned pain modulation paradigms for research settings, while single and double ischemic occlusion seem to be more useful for clinical settings. Influencing factors to be considered are gender, age, stress, physical activity, perceived pain and attentional focus to the conditioning stimulus, but depend on the test site and exerted method., Significance: Hot water immersion, cold pressor test, and single and double ischemic occlusion result in comparable CPM-effects at the mm. trapezius and quadriceps. Anti-nociceptive effects of the cold pack are mainly a result of attention towards the cold pack. Chronic stress, attentional focus towards the conditioning stimulus and perceived pain of the conditioning stimulus influenced the anti-nociceptive effects at the m. trapezius. Gender and level of physical activity influenced the anti-nociceptive effects with the other methods at the m. quadriceps., (© 2020 European Pain Federation - EFIC®.)

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.

Objectives: The nociceptive flexion reflex (NFR) is a spinal reflex induced by painful stimuli resulting in a withdrawal response. Research has shown that the NFR is inhibited through endogenous pain inhibitory mechanisms, which can be assessed by conditioned pain modulation (CPM) paradigms. Although accumulating research suggests that the NFR can be affected by CPM, no clear overview of the current evidence exists. Therefore, the present review aimed at providing such a synthesis of the literature. In addition, the influence of personal factors on the CPM of the NFR was investigated., Materials and Methods: A systematic review was performed and reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using predefined inclusion criteria. Risk of bias was investigated according to the modified Newcastle-Ottawa Scale. Levels of evidence and strength of conclusion were assigned following the guidelines of the Dutch Institute for Healthcare Improvement., Results: Forty articles were included. There is some evidence that CPM produced by thermal or mechanical stimuli induces inhibitory effects on the NFR. However, inconclusive evidence exists with regard to the effect of electrical conditioning stimuli. While several personal factors do not affect CPM of the NFR, increased cognitive interference is associated with reduced NFR inhibition., Discussion: The present review demonstrates that certain types of nociceptive conditioning stimuli have the potential to depress, at the spinal level, nociceptive stimuli elicited from distant body regions. Although CPM of the NFR seems to be robust to the influence of several personal factors, it can be affected by cognitive influences.

The present study aims at studying interactions between cognitive performance and conditioned pain modulation in patients with chronic whiplash-associated disorders (WAD) and healthy controls. In addition, the relation between cortisol concentrations and cognitive performance will be studied in patients with chronic WAD. Thirty-one subjects, 16 healthy subjects and 15 patients with chronic WAD, were enrolled and subjected to several self-report and physiological measures. Self-report measures encompassed pain rating during a procedure evaluating conditioned pain modulation. Afterward, they were subjected to physiological measures, which are cognitive tests (Stroop task, psychomotor vigilance task, and operation span task) preceded and followed by salivary cortisol concentration measurements. Chronic WAD patients performed worse in recall at the operation span task and presented longer reaction times at the psychomotor vigilance task and at the Stroop task when sleep-related words were shown (p < .05). Conditioned pain modulation and cortisol concentrations were not significantly different between patients and controls (p > .05). Only in the healthy subjects, conditioned pain modulation and baseline cortisol concentrations were correlated to cognitive performance (p < .05). This is the first study addressing the relation between pain inhibition and cognitive performance in chronic WAD. We did not reveal impaired pain inhibition but did reveal cognitive dysfunctions in patients with chronic WAD. In healthy subjects, pain inhibition was related to cognitive performance but not in the patient group.

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.)

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.)

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.