Abstract

BackgroundPhysiological fatigue can be defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity. A typical example of a fatigue-related disorder is chronic fatigue syndrome (CFS), a disabling condition of unknown etiology and with uncertain therapeutic options. Recent advances in elucidating pathophysiology of this disorder revealed hypofunction of the hypothalamic-pituitary-adrenal axis and that fatigue in CFS patients appears to be associated with reduced motor neurotransmission in the central nervous system (CNS) and to a smaller extent with increased fatigability of skeletal muscle. There is also some limited evidence that CFS patients may have excessive serotonergic activity in the brain and low opioid tone.Presentation of the hypothesisThis work hypothesizes that repeated cold stress may reduce fatigue in CFS because brief exposure to cold may transiently reverse some physiological changes associated with this illness. For example, exposure to cold can activate components of the reticular activating system such as raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons. Cold stress has also been shown to reduce the level of serotonin in most regions of the brain (except brainstem), which would be consistent with reduced fatigue according to animal models of exercise-related fatigue. Finally, exposure to cold increases metabolic rate and transiently activates the hypothalamic-pituitary-adrenal axis as evidenced by a temporary increase in the plasma levels of adrenocorticotropic hormone, beta-endorphin and a modest increase in cortisol. The increased opioid tone and high metabolic rate could diminish fatigue by reducing muscle pain and accelerating recovery of fatigued muscle, respectively.Testing the hypothesisTo test the hypothesis, a treatment is proposed that consists of adapted cold showers (20 degrees Celsius, 3 minutes, preceded by a 5-minute gradual adaptation to make the procedure more comfortable) used twice daily.Implications of the hypothesisIf testing supports the proposed hypothesis, this could advance our understanding of the mechanisms of fatigue in CFS.

Highlights

  • Physiological fatigue can be defined as a reduction in the force output and/or energygenerating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity

  • There seems to be no universally accepted definition of biological fatigue [1], it is often defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity [1,2,3,4]

  • Fatigue is thought to be associated with a diminished contractile ability of muscles due to accumulation of lactic acid and depletion of energy stores [5,6] as well as with a reduction in motor neurotransmission delivered to skeletal muscle by the central nervous system (CNS), all of which can result in diminished force output [7,8]

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Summary

Background

There seems to be no universally accepted definition of biological fatigue [1], it is often defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity [1,2,3,4]. Cold stress appears to stimulate activity of serotonergic neurons of raphe nuclei [84,8991] and noradrenergic neurons of locus ceruleus [84,92], the situation that would be consistent with activation of behavior and enhanced somatomotor function of the brain [9,87,93,94,95,96] This could be beneficial in CFS because abnormally high fatigability of CFS patients appears to be mediated by a reduction in the ability of the CNS to generate motor neurotransmission [21,22,23]. If statistically significant studies confirm (or refute) the hypothesis, this could further our understanding of the mechanisms of physiological fatigue and possibly contribute to the development of new therapeutic approaches to CFS

Gandevia SC
11. Sandyk R
19. Chronic fatigue syndrome
89. Dickenson AH
94. Lovick TA
96. Hornung JP
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