The mechanism that causes high-performance athletes to "feel the burn" turns out to be the culprit in what makes people with chronic fatigue syndrome feel exhausted by the most common daily activities, new University of Florida Health research shows. Published in the February issue of the journal Pain, the study shows that the neural pathways that transmit feelings of fatigue to the brain might be to blame. In those with chronic fatigue syndrome, the pathways do their job too well. The findings also provide evidence for the first time that peripheral tissues such as muscles contribute to feelings of fatigue. Determining the origins of fatigue could help researchers develop therapies or identify targets for those therapies. Researchers focused on the role of muscle metabolites, including lactic acid and adenosine triphosphate, or ATP, in the disease. The study has demonstrated for the first time that these substances, released when a person exercises his or her muscles, seem to activate these neural pathways. Also, UF Health researchers have shown that these pathways seem to be much more sensitive in patients with chronic fatigue syndrome than in patients without the disease, something that hasn't been studied before. Chronic fatigue syndrome, which the Institute of Medicine recently renamed systemic exertion intolerance disease, or SEID, is characterized by extreme chronic fatigue. Because its chief symptom -- fatigue -- is often associated with many other diseases, it can be difficult to diagnose SEID for the more than 1 million people who actually have the disease, according to the Centers for Disease Control and Prevention. The disease has no root medical cause, and researchers don't know what triggers it. But they are studying aspects of the disease to figure out ways to treat it.
"What we have shown now, that has never been shown before in humans, is that muscle metabolites can induce fatigue in healthy people as well as patients who already have fatigue," said Dr. Roland Staud, a professor of rheumatology and clinical immunology in the UF College of Medicine and the paper's lead author. During exercise, muscles produce metabolites, which are sensed by metaboreceptors that transmit information via fatigue pathways to the brain, according to the researchers. But in patients with SEID, these fatigue pathways have become highly sensitive to metabolites and can trigger excessive feelings of fatigue. "For most of us, at the end of strenuous exertion we feel exhausted and need to stop -- but we will recover rapidly," Staud said. "However, these individuals tire much more rapidly and sometimes just after moving across a room, they are fully exhausted. This takes a toll on their lives. Hypersensitive fatigue pathways play an important role for the often pronounced exercise-related fatigue of patients with the disease". "The take-home message here is, like many of the pain studies we have conducted, there are both peripheral and central nervous system factors at play in these complex syndromes," said Robinson, who is also the director of the UF Center for Pain Research and Behavioral Health. "Our study seems to highlight the important role of these peripheral tissues." Reference: Nkaku Kisaalita, Roland Staud, Robert Hurley, Michael Robinson. Placebo use in pain management: The role of medical context, treatment efficacy, and deception in determining placebo acceptability. Pain, 2014; 155 (12): 2638 DOI: 10.1016/j.pain.2014.09.029