Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects

• Published in: The journal of pain Vol. 10; no. 10; pp. 1099 - 1112
• Main Authors: Light, Alan R, White, Andrea T, Hughen, Ronald W, Light, Kathleen C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2009
• Subjects: Acid Sensing Ion Channels; Adult; Anesthesia & Perioperative Care; ASIC; Catechol O-Methyltransferase - genetics; Catechol O-Methyltransferase - metabolism; Exercise Test; Exercise Tolerance - physiology; Fatigue; Fatigue Syndrome, Chronic - genetics; Fatigue Syndrome, Chronic - immunology; Fatigue Syndrome, Chronic - physiopathology; Female; Fibromyalgia - genetics; Fibromyalgia - immunology; Fibromyalgia - physiopathology; gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Genetic Predisposition to Disease - genetics; Humans; Immune System - metabolism; Immune System - physiopathology; Interleukin-10 - genetics; Interleukin-10 - metabolism; leukocytes; Male; Middle Aged; muscle pain; Pain Medicine; Receptors, Adrenergic - genetics; Receptors, Adrenergic - metabolism; Receptors, Adrenergic, beta-2 - genetics; Receptors, Adrenergic, beta-2 - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Purinergic - genetics; Receptors, Purinergic - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Sensory Receptor Cells - immunology; Sensory Receptor Cells - metabolism; Sodium Channels - genetics; Sodium Channels - metabolism; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; TRPV1; muscle pain; Fatigue; leukocytes; ASIC; TRPV1; gene expression
• DOI: 10.1016/j.jpain.2009.06.003
• ISSN: 1526-5900; 1528-8447

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 β-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 α-2A, β-1, β-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.