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Aims: The inflammatory reflex is defined by action potentials transmitted in the vagus nerve that regulate TNF production in the spleen during endotoxemia. Detailed molecular mechanistic studies implicate the vagus nerve, the splenic nerve, a T cell subset the produces acetylcholine under the control of adrenergic signals, and alpha7 nAChR expressed on macrophages. This study defines the vagus nerve fibers that transmit the efferent signal in this pathway, a motor arc of the inflammatory reflex. Methods: Mice and rats were subjected to electrical cervical vagus nerve stimulation or sham surgery. Cytokine levels in serum were measured in endotoxemic animals or in endotoxin-exposed blood samples. In select animals, evoked potentials were measured in the vagus nerve, and a portion of the vagus nerve was anesthetized using local application of lidocaine before stimulation. Results: The lowest threshold subdiaphragmatic fibers in the rat vagus nerve have conduction velocities in the range of myelinated B fibers. The stimulation current threshold for significant suppression of serum TNF levels was similar in mice and rats (≤500 µA). Blockade of the fibers caudal to the site of vagus nerve stimulation impaired the inhibition of TNF release. A single suprathreshold pulse stimulation is sufficient to suppress TNF release in endotoxemia. Conclusion: These results indicate that single-pulse and unidirectional electrical activation of the cervical vagus nerve reduces TNF in endotoxemia.
Olofsson, P. S., Levine, Y. A., Caravaca, A., Chavan, S. S., Pavlov, V. A., Faltys, M., & Tracey, K. J. (2015). Single-Pulse and Unidirectional Electrical Activation of the Cervical Vagus Nerve Reduces Tumor Necrosis Factor in Endotoxemia. Bioelectronic Medicine, 2(1), 37–42. https://doi.org/10.15424/bioelectronmed.2015.00006