Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects - PubMed (original) (raw)

Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

Alan R Light et al. J Pain. 2009 Oct.

Abstract

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS. We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes. Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain. These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

Perspective: Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.

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Figures

Figure 1

Figure 1

Ratings of Mental Fatigue, Physical Fatigue, and Pain at the times indicated. Ratings were based on a 0-100 scale from none to the worst the patient could even imagine experiencing. Base = before exercise; MidEx = at midpoint of 25 minute exercise (min 13); 0.5 = one half hour after end of exercise; 8 = 8 hours after exercise; 24 = 24 hours after exercise; 48 = 48 hours after exercise.

Figure 2

Figure 2

Amount of mRNA for ASIC3, P2X4, P2X5, and TRPV1 expressed as fold increases relative to baseline levels at each of the times indicated before (baseline) and after the end of 25 minutes of moderate exercise. * Indicates P< 0.05 compared to control subjects for the area under curve (AUC) of mRNA across all time points after exercise. Faint dotted line indicates the baseline levels.

Figure 3

Figure 3

Amount of mRNA for α-2A, β-1, β-2 adrenergic receptors and catechol-o-methyl-transferase (COMT) relative to baseline levels. * Indicates P< 0.05 compared to control subjects for the area under curve (AUC) of mRNA across all time points after exercise. Faint dotted line indicates the baseline levels.

Figure 4

Figure 4

Amount of mRNA for IL6, TNFα, IL10, TLR4, CD14 relative to baseline levels. * Indicates P< 0.05 compared to control subjects for the area under curve (AUC) of mRNA across all time points after exercise. Faint dotted line indicates the baseline levels.

Figure 5

Figure 5

Point plots of AUC for sum of 4 genes (P2X4, β-1, β-2, and IL10) (left) and 9 genes (ASIC3, P2X4, β-1, β-2, COMT, IL10, TLR4, and CD14) (right). All data converted to Log base 10 so the points could be plotted together. Dotted lines indicate the lowest values for CFS-FMS patients, indicating little overlap with Control Subjects.

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