title: Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis.
abstract: 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.
authors.affiliation: Tufts University Psychology, Massachusetts General Hospital Psychiatric Neuroscience, 490 Boston Avenue, Medford, MA 02155, USA. michael.vanelzakker@gmail.com
authors.forename: Michael B
authors.initials: MB
authors.lastname: VanElzakker
mesh_terms: D002450:Cell Communication / Q000502:physiology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D055809:Illness Behavior / Q000502:physiology*; D008954:Models, Biological; D020421:Vagus Nerve Diseases / Q000150:complications* / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D016207:Cytokines