Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia

To begin to elucidate the mechanisms underlying the benefits of exercise for chronic pain, we assessed the influence of exercise on brain responses to pain in fibromyalgia (FM). Complete data were collected for nine female FM patients and nine pain-free controls (CO) who underwent two functional neuroimaging scans, following exercise (EX) and following quiet rest (QR). Brain responses and pain ratings to noxious heat stimuli were compared within and between groups. For pain ratings, there was a significant (p \u3c 0.05) Condition by Run interaction characterized by moderately lower pain ratings post EX compared to QR (d = 0.39–0.41) for FM but similar to ratings in CO (d = 0.10–0.26), thereby demonstrating that exercise decreased pain sensitivity in FM patients to a level that was analogous to pain-free controls. Brain responses demonstrated a significant within-group difference in FM patients, characterized by less brain activity bilaterally in the anterior insula following QR as compared to EX. There was also a significant Group by Condition interaction with FM patients showing less activity in the left dorsolateral prefrontal cortex following QR as compared to post-EX and CO following both conditions. These results suggest that exercise appeared to stimulate brain regions involved in descending pain inhibition in FM patients, decreasing their sensitivity to pain. Thus, exercise may benefit patients with FM via improving the functional capacity of the pain modulatory system

Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p \u3c 0.05). Patients and controls had similar physiological responses to exercise (p \u3e 0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p \u3c 0.05). For cognitive performance, a significant Group by Time interaction (p \u3c 0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p \u3c 0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p \u3c 0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices. Changes in brain activity were significantly related to symptoms for patients (p \u3c 0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer’s disease

Introduction: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer\u27s disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer\u27s disease (AD). Methods: Eighty‐six enrollees from the Wisconsin Registry for Alzheimer\u27s Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T‐1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). Results: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. Summary: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific

Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia

To begin to elucidate the mechanisms underlying the benefits of exercise for chronic pain, we assessed the influence of exercise on brain responses to pain in fibromyalgia (FM). Complete data were collected for nine female FM patients and nine pain-free controls (CO) who underwent two functional neuroimaging scans, following exercise (EX) and following quiet rest (QR). Brain responses and pain ratings to noxious heat stimuli were compared within and between groups. For pain ratings, there was a significant (p d = 0.39–0.41) for FM but similar to ratings in CO (d = 0.10–0.26), thereby demonstrating that exercise decreased pain sensitivity in FM patients to a level that was analogous to pain-free controls. Brain responses demonstrated a significant within-group difference in FM patients, characterized by less brain activity bilaterally in the anterior insula following QR as compared to EX. There was also a significant Group by Condition interaction with FM patients showing less activity in the left dorsolateral prefrontal cortex following QR as compared to post-EX and CO following both conditions. These results suggest that exercise appeared to stimulate brain regions involved in descending pain inhibition in FM patients, decreasing their sensitivity to pain. Thus, exercise may benefit patients with FM via improving the functional capacity of the pain modulatory system.This article is from Brain Sci. 2016, 6(1), 8; doi:10.3390/brainsci6010008. Posted with permission.</p

Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging. Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 min of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 h following exercise. Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p 0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p This accepted article is published as Cook D, Light A, Light K, Broderick G, Shields M, Dougherty R, Meyer J, VanRiper S, Stegner A, Ellingson L, Vernon S (2017). Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain, Behavior & Immunity, 62; 87-99. doi: 10.1016/j.bbi.2017.02.009. </p

Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise

Background: Consensus for an operational definition of post-exertion malaise (PEM) and which symptoms best characterize PEM has not been established and may be due to variability within and between studies. Purpose: Determine the magnitude of the effect of maximal and submaximal physical exertion on multiple myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms that are associated with PEM and explore variability among two studies in which mood, fatigue, and pain symptoms were measured before and after exercise. Methods: Symptoms were measured before, and 48 and 72 hours after exercise in study 1 (ME/CFS = 13; Controls = 11) and before and 24 hours after exercise in study 2 (ME/CFS = 15, Controls = 15). Between-study variability was examined by comparing Hedges d effect sizes (95% CI) from studies 1 and 2. Within-patient group variability was examined via inspection of dot density plots. Results: In study 1, large increases in general fatigue (Δ = 1.05), reduced motivation (Δ = 0.93), feelings of fatigue (Δ = 0.90), feelings of confusion (Δ = 0.93), and total mood disturbance (Δ = 0.90) were found at 72 hours. In study 2, a large increase in affective/sensory pain (Δ = 0.79) was found at 24 hours. Dot density plots in both studies revealed substantial variability among people with ME/CFS relative to healthy control participants. Conclusions: PEM symptoms are variable among people with ME/CFS and several gaps in the literature need to be addressed before guidelines for measuring PEM in the clinical or research setting can be established.This article is published as Lindheimer J, Meyer J, Stegner A, Rougherty R, Van Riper S, Shields M, Reisner A, Shukla S, Light A, Yale S, Cook D (2017). Symptom variability following acute exercise in ME/CFS: A perspective on measuring post-exertion malaise. Fatigue: Biomedicine, Health & Behavior, 5(2); 69-88. doi: 10.1080/21641846.2017.1321166.</p

Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness

Background: Post-exertional malaise (PEM) is considered a characteristic feature of chronic multi-symptom illnesses (CMI) like Gulf War illness (GWI); however, its pathophysiology remains understudied. Previous investigations in other CMI populations (i.e., Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) have reported associations between PEM and expression of genes coding for adrenergic, metabolic, and immune function. Objectives: To investigate whether PEM is meditated by gene expression in Veterans with GWI. Methods: Veterans with GWI (n = 37) and healthy control Gulf War Veterans (n = 25) provided blood samples before and after 30-min of cycling at 70% of age-predicted heart rate reserve. Relative quantification of gene expression, symptom measurements, and select cardiopulmonary parameters were compared between groups at pre-, 30 minpost-, and 24 hpost-exercise using a doubly multivariate repeated measures analysis of variance (RM-MANOVA). Mediation analyses were used to test indirect effects of changes in gene expression on symptom responses (i.e., PEM) to the standardized exercise challenge. Results: Veterans with GWI experienced large symptom exacerbations following exercise compared to controls (Cohen's d: 1.65; p < 0.05). Expression of β-actin (ACTB), catechol-O-methyltransferase (COMT), and toll-like receptor 4 (TLR4) decreased in Veterans with GWI at 30 min (p < 0.05) and 24 h post-exercise (p < 0.05). Changes in gene expression did not mediate post-exercise symptom exacerbation in GWI (Indirect Effect Slope Coefficient: 0.06 – 0.02; 95% CI: 0.19, 0.12). Conclusion: An acute bout of moderate intensity cycling reduced the expression of select structural, adrenergic, and immune genes in Veterans with GWI, but the pathophysiological relevance to PEM is unclear