Post-Exercise Fatigue and Pain Correlate with Gene Expression Alterations in Patients with Chronic Fatigue Syndrome

Post-Exercise Fatigue and Pain Correlate with Gene Expression Alterations in Patients with Chronic Fatigue Syndrome

shutterstock_233899279Researchers at the University of Utah published in the Journal of Internal Medicine their findings that moderate physical exercise can induce changes in gene expression that correlate with self-reported pain and fatigue in patients with chronic fatigue syndrome (CFS). The study is entitled “Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.

CFS is a complex disorder characterized by extreme, remitting/relapsing fatigue that interferes with a person’s well-being and is not relieved by rest or recovery. Other symptoms include post-exertional malaise, muscle and/or joint pain, headaches, loss of memory/concentration, sore throat, enlarged lymph nodes and unrefreshing sleep. Up to 70% of individuals experiencing CFS meet the criteria for fibromyalgia, a medical disorder characterized by widespread chronic musculoskeletal pain, fatigue, stiffness and numbness in certain parts of the body, headaches, sleep disorder and mood alterations. Fibromyalgia can affect people’s ability to conduct simple daily tasks, also compromising their quality of life.

The research team had previously identified in white blood cells molecular receptors involved in sensory neuron signaling of muscle pain and fatigue. In this study, the team aimed at analyzing differences in messenger RNA (mRNA) expression for genes linked to signaling and modulating sensory fatigue and muscle pain in patients with CFS and fibromyalgia at two points, baseline rest and after moderate exercise for 25 minutes on a stationary bicycle. In total, 48 CFS patients with or without co-occurring fibromyalgia, 18 patients with fibromyalgia only, and 49 healthy controls were evaluated. Researchers assessed fatigue and pain and collected blood samples at baseline and at 0.5, 8, 24 and 48 hours after exercise. White blood cells were isolated from the blood and analyzed for mRNA expression levels of 13 genes known to be involved in sensory, adrenergic and immune functions.

Researchers found that, different from healthy controls, both groups of patients reported an increase in fatigue and pain throughout the 48 hours period after exercise. 71% of the CFS patients, with or without fibromyalgia, had an increase in mRNA levels from 12 out of the 13 genes analyzed after exercise, which was in agreement with the behavioral measures of fatigue and pain recorded. The remaining CFS patients (29%) were found to experience a decrease in expression of the adrenergic alpha 2A receptor upon exercise, which was linked to a clinical history of orthostatic intolerance (related to symptoms like dizziness, headache, altered vision, weakness and heart palpitations that are felt when standing upright, and which are relieved when sitting down).

No significant changes in gene expression were found in the controls. Interestingly, patients with fibromyalgia and not CFS had no exercise-induced changes in gene expression, different from the self-reported fatigue and pain measures. The baseline level for various key genes was, however, already abnormal in these patients; nonetheless, the expression profile was clearly different from healthy controls and CFS patients at baseline, where higher mRNA levels for certain genes were found.

Researchers concluded that upon moderate exercise, gene expression suffers alterations especially in CFS patients, with an increase in specific sensory, adrenergic and immune genes that was not found in healthy individuals. The team suggests that these genes could potentially be used as biomarkers for CFS.