Available online 18 June 2013
Chronic fatigue syndrome from vagus nerve infection: A psychoneuroimmunological hypothesis
Michael B. VanElzakker
Tufts University Psychology, Massachusetts General Hospital Psychiatric Neuroscience, 490 Boston Avenue, Medford, MA 02155, USA
http://dx.doi.org/10.1016/j.mehy.2013.05.034, How to Cite or Link Using DOI
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Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found.
In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve.
When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS. The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria.
Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.
Fig. 1. A highly simplified schematic of vagus nerve anatomy. Circles represent ganglia and paraganglia, which contain both glial cells and sensory vagus nerve chemoreceptors. A viral or bacterial infection within any ganglia or paraganglia causes glial activation, leading to the release of proinflammatory cytokines and other neuroexcitatory mediators. The resulting afferent signal enters the brain at the nucleus tractus solitarius (NTS), and triggers sickness behaviors. When normal glial cell activation becomes pathological as it does in neuropathic pain conditions, the signal is intensified and intractable, leading to CFS.
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