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.
Key words
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Article info
Publication history
Published online: August 03, 2009
Accepted:
June 1,
2009
Received in revised form:
May 10,
2009
Received:
March 30,
2009
Footnotes
Supported by NIH grant R21 NS057821 from NINDS and NIAMS, with additional ancillary support from NIH R21 AT0002209 from NCAM, a Catalyst grant from the University of Utah Health Sciences Center, and the Department of Anesthesiology, University of Utah.
Identification
Copyright
© 2009 American Pain Society. Published by Elsevier Inc. All rights reserved.
