Pain-Fatigue Link May Explain Why FM, CFS Are More Prevalent in Women:
The marked predominance of chronic pain and fatigue conditions like fibromyalgia and chronic fatigue syndrome (CFS) in women may be in part because an acid sensing ion channel (ASIC3) activated by decreases in extracellular pH works with testosterone to protect males against fatigue. University of Iowa researchers led by Kathleen Sluka, PT, PhD, from the graduate program in physical therapy and rehabilitation science, reported the discovery in animal studies published early online in American Journal of Physiology – Regulatory, Integrative, and Comparative Physiology.1
“The differences in fatigue between males and females depend on both the presence of testosterone and the activation of ASIC3 channels, which suggest that they are interacting somehow to protect against fatigue. These differences may help explain some of the underlying differences we see in chronic pain conditions that include fatigue…predominantly [found in] women [than] men,” Dr. Sluka said.
The researchers first used knock-out mice lacking ASIC3 to measure differences in exercise-induced muscle fatigue. They had previously shown that decreases in extracellular pH activate ASIC3 and cause pain. Exercise-induced lactic acid is the cause of reduced pH in the exercising animal. Wildtype mice with normal ASIC3 were less fatigued than female mice by a task involving three 1-hour runs on a treadmill. Fatigue was measured by temporary loss of muscle strength, whereby the mice fell off the apparatus.
In mice without ASIC3, males were fatigued just as quickly as females. Boosting testosterone with sc injections gave the female wildtype (ASIC3 +/+) mice as much stamina as the normal males but had little effect on the females lacking the ASIC3 protein. The study suggests that muscle pain and fatigue may share a common pathway that is disrupted in chronic muscle pain conditions.
Dr. Sluka noted that up to 76% of patients with chronic widespread musculoskeletal pain report fatigue and that up to 94% of patients with CFS report muscle pain. “This type of fatigue is common in several chronic pain conditions including fibromyalgia, osteoarthritis, and rheumatoid arthritis. Our long-term goal is to come up with better treatment for chronic musculoskeletal pain. But the fatigue that is typically associated with chronic widespread pain is also a big clinical problem. It leaves people unable to work or engage in social activities. If we could find a way to reduce fatigue, we could really improve quality of life for these patients.”
Reference
1. Burnes LA, Kolker SJ, Danielson JF, et al. Enhanced muscle fatigue occurs in male but not female ASIC -/- mice [published online ahead of print February 27, 2008]. Am J Physiol Regul Integr Comp Physiol. 2008; doi:10.1152/ajpregu.00687.2007. http://ajpregu.physiology.org/cgi/content/abstract/294/4/R1347.
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