Defining Fatigue

The problem in trying to figue out CFS is that we don't even know what fatigue is. Its definition ranges from emotion to bodily sensation to sluggishness. It's no wonder the lerthargy caused by mental depression is lumped into fatigue and physicians used to confuse CFS with depression.

Calling it an effort required to peform task is yet  another way to define it. As you exercise, your body gets stressed. As it gets stressed, you have to put more effort to maintain the same level of performance. Tanaka et. al. defines fatigue in their paper "Frontier Studies on Fatigue.." as follows:

Fatigue is defined as a condition or phenomenon of decreased ability and efficiency of mental and/or physical activities, caused by excessive mental or physical activities, diseases, or syndromes. It is often accompanied by a peculiar sense of discomfort, a desire to rest, and reduced motivation, referred to as fatigue sensation. 

They go on to discuss faciliator/inhibitor system that regulates the performance and homeostasis. In summary, as the body gets stressed, the facilitator increases the afferent motor signal to maintain the performance. At the same time, the inhibitor generates the bodily sensation of fatigue to prevent you from damaging the body by further stressing. They claim that, in CFS patients, the facilitator is broken and the inhibitor becomes over-sensitive because of the repeated or continuous over-stressing. With the inhibitor functioning without the corresponding facilitator, they quickly sucumb to fatigue sensation.

Are they right? Who knows. It could be yet another "geo-centric" theory of CFS. An alternative explanation would be an amplified stress signal. The brain must receive the efferent signal from the body to detect the stress, and that signal could be amplified or the brain is over-sensitive to it. There are papers reporting gene expression changes at the receptor level, so the amplification could be happening at the receptor level. There are also papers reporting changes in brain regions responsible for fatigue, so the amplication could be in the brain as well.  If verified, any of these theories could point to pathophysiology, and therefore possible treatment, of CFS.