Cancer-related fatigue (C-rF) is a debilitating symptom that affects around one-third of people for months or years after cancer treatment. While the etiology of C-rF remains uncertain, it has been demonstrated that cancer survivors with C-rF display impaired exercise tolerance compared with those without C-rF, with the degree of exercise intolerance associated with chronic fatigue severity. Exercise intolerance in cancer survivors with C-rF likely contributes to reported difficulties in performing activities of daily living, as well as impaired quality of life. Thus, understanding the physiological (e.g., cardiopulmonary, metabolic and neuromuscular) alterations contributing to impaired exercise tolerance in people with C-rF is of importance, particularly given that these impairments could be reversible through exercise training.
One physiological alteration that could hinder the ability to perform activities of daily living is neuromuscular fatigability, defined as the reduction in neuromuscular function in response to exercise. To gain a better understanding of the etiology of neuromuscular fatigability in cancer survivors with C-rF, our study, published in Medicine and Science in Sports and Exercise®, assessed the mechanisms of neuromuscular fatigability in cancer survivors with and without C-rF. We recruited 96 cancer survivors and separated the participants into two groups (fatigued and non-fatigued) based on a clinical cut-point for the diagnosis of chronic fatigue. In response to incremental cycling stages interspersed with measures of neuromuscular function, neuromuscular fatigability was assessed through changes in maximal voluntary contraction force of the knee extensors. The mechanisms of reduced maximal contraction force were determined through electrical stimulations either superimposed to voluntary contractions (capacity of the nervous system to activate muscle) or evoked on relaxed muscles (their contractility). Moreover, power outputs during cycling were expressed relative to gas exchange thresholds to determine the relative intensity of exercise.
Our results demonstrated that the magnitude and rate of decrements in neuromuscular function was substantially greater in the fatigued versus non-fatigued group. For example, following just 3 minutes of exercise at a low absolute (~20-25 W) and relative power output (47% of the gas exchange threshold), the fatigued group demonstrated decrements to maximal muscle force generating capacity that were five times greater than the non-fatigued group (−10% vs −2% on average, respectively). The responses to electrically evoked contractions revealed that mechanisms residing in the muscle were primarily responsible for the greater fatigability in the fatigued group.
The rapid and profound decrements in neuromuscular function we found in response to low-intensity exercise in those with C-rF was striking. Such a rapid decline in neuromuscular function in response to exercise of low power output has potentially important implications for the physiological and perceptual impact of typical activities of daily living. For example, the low intensity during the initial stages of cycling is likely to correspond with activities such as walking, housework, gardening or slowly climbing stairs. Accordingly, impaired neuromuscular fatigability, owing to rapid perturbations in the muscle, might represent an important contributor to the regularly reported difficulties in performing physical tasks of daily living in those with C-rF.
Dr. Callum Brownstein (@CGBrownstein) is a postdoctoral researcher at University Jean Monnet, Saint Etienne, France. He completed his Ph.D. at Northumbria University, Newcastle, U.K., where he assessed recovery of neuromuscular function following high-intensity intermittent exercise. His current research focuses on the acute integrative response to whole-body exercise in athletes, healthy active and clinical populations, with a focus on neuromuscular perturbations.
Dr. Guillaume Millet (@kinesiologui) is a professor of exercise physiology at University Jean Monnet, Saint-Etienne, France. After graduating from the University of Franche-Comte in 1997, he held various positions in Dijon, Saint-Etienne and Grenoble. Between 2013 and 2018, he was professor in the Human Performance Laboratory and the Faculty of Kinesiology at the University of Calgary (Canada), where he led a research group on neuromuscular fatigue. In 2019, he was named at the Institut Universitaire de France as a senior member. His general research area investigates the physiological, neurophysiological and biomechanical factors associated with fatigue, both in extreme exercise (ultra-endurance) and patients (neuromuscular diseases, cancer, multiple sclerosis, ICU).
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