Document Type


Original Publication Date


Journal/Book/Conference Title

Behavioral and Brain Functions

DOI of Original Publication



Originally published at

Date of Submission

August 2014


Background Physiological 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 hypothesis This 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 hypothesis To 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 hypothesis If testing supports the proposed hypothesis, this could advance our understanding of the mechanisms of fatigue in CFS.


© 2007 Shevchuk; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Is Part Of

VCU Radiation Oncology Publications

1744-9081-3-55-s1.pdf (37 kB)
Sympathetic nervous system and chronic fatigue syndrome. The file name is Additional_File_1.pdf and it contains a brief review of literature on the sympathetic nervous system abnormalities observed in patients with chronic fatigue syndrome. The file contains its own list of references separate from the main text.

1744-9081-3-55-s2.pdf (105 kB)
Proposed study design. The file name is Additional_File_2.pdf and it contains a detailed protocol of the proposed study including statistical estimates of the sample size. The file contains its own list of references separate from the main text.

1744-9081-3-55-s3.pdf (47 kB)
Limited preliminary evidence. The file name is Additional_File_3.pdf and it provides a detailed description of preliminary evidence that appears to support the hypothesis. The file contains its own list of references separate from the main text.