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Med Hypotheses. 2010 Aug;75(2):244-9. doi: 10.1016/j.mehy.2010.02.032. Epub 2010 Mar 24.

A new hypothesis of chronic fatigue syndrome: co-conditioning theory.

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Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.


Chronic fatigue syndrome is an illness characterized by a profound, disabling, and unexplained sensation of fatigue lasting at least 6 months, which severely impairs daily functioning and is accompanied by a combination of non-specific symptoms. Many potential causes of chronic fatigue syndrome have been investigated, including viral infections, immune dysfunctions, abnormal neuroendocrine responses, central nervous system abnormalities, autonomic dysfunctions, impaired exercise capacities, sleep disruptions, genetic backgrounds, psychiatric abnormalities, personality, and abnormal psychological processes. However, no etiology, specific physical signs or laboratory test abnormalities have been found. It is essential to establish a conceptual theory of chronic fatigue syndrome that can explain its pathophysiology in order to identify the clinical entity and to develop effective treatment methods. In this article, a new conceptual hypothesis about the pathophysiology of chronic fatigue syndrome, the co-conditioning theory, is presented: after repetitive overwork and/or stress, alarm signal to rest and fatigue sensation may cause in response to an unconditioned stimulus (impaired homeostasis and function) that has been paired with a conditioned stimulus (overwork and/or stress). In the future, a new treatment strategy for patients with chronic fatigue syndrome, re-co-conditioning therapy, may be developed on the basis of the co-conditioning theory. In addition, this theory will likely contribute to a better understanding of the pathophysiology of chronic fatigue syndrome.

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