During disease, infection, or trauma, the cytokine tumor necrosis factorα (TNF α) causes fever, fatigue, malaise, allodynia, anorexia, gastric stasis associated with nausea, and emesis via interactions with the central nervous system. Our studies have focused on how TNFα produces a profound gastric stasis by acting on vago-vagal reflex circuits in the brainstem. Sensory elements of this circuit (i.e., nucleus of the solitary tract [NST] and area postrema) are activated by TNFα. In response, the efferent elements (i.e., dorsal motor neurons of the vagus) cause gastroinhibition via their action on the gastric enteric plexus. We find that TNFα
presynaptically modulates the release of glutamate from primary vagal afferents to the NST and can amplify vagal afferent responsiveness by sensitizing presynaptic intracellular calcium-release mechanisms. The constitutive presence of TNFα receptors on these afferents and their ability to amplify afferent signals may explain how TNF α can completely disrupt autonomic control of the gut. NEUROSCIENTIST 14(1):53—67, 2008. DOI: 10.1177/1073858407305725
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