Muscle Fatigue in Health and Disease

An untrained couch potato involuntarily forced to undergo a long strenuous exercise towards exhaustion will feel it at the end as a discomforting fatigue. A well-trained athlete will feel the same but after a longer time. Patients of various neurological diseases will do so much earlier. All may also finally experience muscle pain and soreness the next day.Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. Muscle fatigability varies with muscle use, age and sex. It is commonly divided into two broad categories: peripheral and central fatigue. The first refers to the many processes in the fatiguing muscle(s), the second to subsequent processes in the central nervous system (CNS). Peripheral muscle fatigue can be caused by numerous different mechanisms, ranging from the accumulation of metabolites within muscle fibers to their damage. Central fatigue involves the inadequacy of the CNS to generate and maintain sufficiently strong motor command. There must of course be a mediator relating the two fatigue types, and this is the collection of small-diameter group III (Aδ) and IV (C) nerve fibers emanating from the muscle and distributing their activation effects throughout the CNS.Muscle fatigue develops during eventually exhausting exercise that goes along with activations of the cardio-vascular and respiratory system to supply oxygen and energy resources. While these functions are supported by a number of sensory afferents, fatigue-activated group III/IV muscle afferents have been proposed to contribute their share to cardio-vascular and ventilatory reflex responses that are mediated in the brainstem. Neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O₂ delivery determine the fatigability of skeletal muscle (Amann 2012).The development of chronic muscle fatigue is related to muscle wasting mediated by aging, myopathies, muscle dystrophies, immobilization, insulin resistance, diseases associated with systemic inflammation (arthritis, sepsis, infections), trauma, cardio-vascular (heart failure) and respiratory disorders (chronic obstructive pulmonary disease (COPD)), chronic kidney failure, multiple sclerosis (MS), and, more recently, coronavirus disease 2019 (COVID-19).