Single-pulse and unidirectional electrical activation of the cervical vagus nerve reduces tumor necrosis factor in endotoxemia
Open accessAbstract
The inflammatory reflex is a neural circuit defined by action potentials transmitted in the vagus nerve that regulate cytokine production in the spleen. Detailed mechanistic studies implicate the vagus nerve, the splenic nerve, a T-cell subset that produces acetylcholine under the control of adrenergic signals, and alpha7 nicotinic acetylcholine receptors (α7nAChR). 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. 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. Evoked potentials were measured in the vagus nerve and a portion of the vagus nerve was anesthetized using local application of lidocaine before stimulation. The lowest threshold subdiaphragmatic fibers in the rat vagus nerve have conduction velocities consistent with that 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 was sufficient to suppress TNF release in endotoxemia. These results indicate that single-pulse and unidirectional electrical activation of the cervical vagus nerve reduce TNF in endotoxemia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous studies of peripheral implants used for rodents have reported peak-to-peak signal amplitudes ranging from 100-900 μV in response to electrical stimuli.
“Previous studies of peripheral implants used for rodents have reported peak-to-peak signal amplitudes ranging from 100–900 μV in response to electrical stimuli [22–27].”
From A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve (2017) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211 · see citing works
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · see citing works
Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228 · see citing works
Self-citationElenkov, I. J., Wilder, R. L., Chrousos, G. P., & Vizi, E. S. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01470-4 · Cited by 2,252 · see citing works
Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit
Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdés-Ferrer, S. I., Levine, Y. A., Reardon, C., Tusche, M. W., Pavlov, V. A., Andersson, U., Chavan, S., et al. (2011) · Science · doi:10.1126/science.1209985 · Cited by 1,551 · see citing works
The vagus nerve and the inflammatory reflex – linking immunity and metabolism
Pavlov, V. A., & Tracey, K. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.189 · Cited by 1,040 · see citing works
Self-citationBacteria activate sensory neurons that modulate pain and inflammation
Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., Wainger, B., Strominger, A., Muralidharan, S., Horswill, A. R., et al. (2013) · Nature · doi:10.1038/nature12479 · Cited by 949 · see citing works
The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation
Pavlov, V. A., Wang, H., Czura, C. J., Friedman, S. G., & Tracey, K. J. (2003) · Molecular Medicine · doi:10.1007/bf03402177 · Cited by 772 · see citing works
Self-citationSplenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia
Rosas‐Ballina, M., Ochani, M., Parrish, W. R., Ochani, K., Harris, Y., Huston, J. M., Chavan, S. S., & Tracey, K. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803237105 · Cited by 757 · see citing works
Beyond Heart Rate Variability: Vagal Regulation of Allostatic Systems
THAYER, J. F., & STERNBERG, E. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1366.014 · Cited by 703 · see citing works
Huston, J. M., Ochani, M., Rosas-Ballina, M., Liao, H., Ochani, K., Pavlov, V. A., Gallowitsch-Puerta, M., Ashok, M., Czura, C. J., Foxwell, B., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052362 · Cited by 683 · see citing works
Dopamine mediates vagal modulation of the immune system by electroacupuncture
Rosas, R. T., Yehia, G., Peña, G., Mishra, P., Thompson-Bonilla, M. D. R., Moreno‐Eutímio, M. A., Arriaga‐Pizano, L., Isibasi, A., & Ulloa, L. (2014) · Nature Medicine · doi:10.1038/nm.3479 · Cited by 633 · see citing works
Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation
Riol‐Blanco, L., Ordovás-Montañés, J., Perro, M., Naval, E., Thiriot, A., Álvarez, D., Paust, S., Wood, J. N., & von Andrian, U. H. (2014) · Nature · doi:10.1038/nature13199 · Cited by 596 · see citing works
A jump-start for electroceuticals
Famm, K., Litt, B., Tracey, K. J., Boyden, E. S., & Slaoui, M. (2013) · Nature · doi:10.1038/496159a · Cited by 554 · see citing works
Pavlov, V. A., Parrish, W. R., Rosas‐Ballina, M., Ochani, M., Gallowitsch‐Puerta, M., Ochani, K., Chavan, S. S., Al‐Abed, Y., & Tracey, K. J. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.06.011 · Cited by 437 · see citing works
Reflex principles of immunological homeostasis
Andersson, U., & Tracey, K. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075015 · Cited by 414 · see citing works
Matteoli, G., Gomez-Pinilla, P. J., Némethová, A., Giovangiulio, M. D., Cailotto, C., van Bree, S. V., Michel, K., Tracey, K., Schemann, M., Boesmans, W., et al. (2013) · Gut · doi:10.1136/gutjnl-2013-304676 · Cited by 412 · see citing works
Rethinking inflammation: neural circuits in the regulation of immunity
Olofsson, P. S., Rosas‐Ballina, M., Levine, Y. A., & Tracey, K. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01138.x · Cited by 393 · see citing works
Self-citationNeural reflexes in inflammation and immunity
Andersson, U., & Tracey, K. J. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120571 · Cited by 379 · see citing works
Effects of Vagal Stimulation on Experimentally Induced Seizures in Rats
Woodbury, D. M., & Woodbury, J. W. (1990) · Epilepsia · doi:10.1111/j.1528-1157.1990.tb05852.x · Cited by 369 · see citing works
Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
Borovikova, L. V., Ivanova, S., Nardi, D., Zhang, M., Yang, H., Ombrellino, M., & Tracey, K. J. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00233-2 · Cited by 322 · see citing works
Arima, Y., Harada, M., Kamimura, D., Park, J.-H., Kawano, F., Yull, F. E., Kawamoto, T., Iwakura, Y., Betz, U. A. K., Márquez, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.022 · Cited by 307 · see citing works
Huston, J. M., Gallowitsch‐Puerta, M., Ochani, M., Ochani, K., Yuan, R., Rosas‐Ballina, M., Ashok, M., Goldstein, R. S., Chavan, S. S., Pavlov, V. A., et al. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000288102.15975.ba · Cited by 306 · see citing works
Elenkov, I. J. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.06.037 · Cited by 273 · see citing works
α7-Cholinergic Receptor Mediates Vagal Induction of Splenic Norepinephrine
Vida, G., Peña, G., Deitch, E. A., & Ulloa, L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003722 · Cited by 257 · see citing works
Levine, Y. A., Koopman, F. A., Faltys, M. A., Caravaca, A. S., Bendele, A. M., Zitnik, R. J., Vervoordeldonk, M. J., & Tak, P. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104530 · Cited by 204 · see citing works
Vagus nerve controls resolution and pro-resolving mediators of inflammation
Mirakaj, V., Dalli, J., Granja, T., Rosenberger, P., & Serhan, C. N. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20132103 · Cited by 176 · see citing works
Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia
Berthoud, H., & Powley, T. L. (1993) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(93)90046-w · Cited by 173 · see citing works
Olofsson, P. S., Katz, D. A., Rosas‐Ballina, M., Levine, Y. A., Ochani, M., Valdés‐Ferrer, S. I., Pavlov, V. A., Tracey, K. J., & Chavan, S. S. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00405 · Cited by 164 · see citing works
Koopman, F. A., Stoof, S. P., Straub, R. H., van Maanen, M. A., Vervoordeldonk, M. J., & Tak, P. P. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00065 · Cited by 155 · see citing works
Origin of noradrenergic innervation of the spleen in rats
Bellinger, D. L., Felten, S. Y., Lorton, D., & Felten, D. L. (1989) · Brain Behavior and Immunity · doi:10.1016/0889-1591(89)90029-9 · Cited by 146 · see citing works
Innervation of the spleen in the rat: Evidence for absence of afferent innervation
Nance, D. M., & Burns, J. (1989) · Brain Behavior and Immunity · doi:10.1016/0889-1591(89)90028-7 · Cited by 145 · see citing works
High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog
Yoo, P. B., Lubock, N. B., Hincapie, J. G., Ruble, S. B., Hamann, J. J., & Grill, W. M. (2013) · Journal of Neural Engineering · doi:10.1088/1741-2560/10/2/026003 · Cited by 133 · see citing works
Cholinergic Neural Signals to the Spleen Down-Regulate Leukocyte Trafficking via CD11b
Huston, J. M., Rosas‐Ballina, M., Xue, X., Dowling, O., Ochani, K., Ochani, M., Yeboah, M. M., Chatterjee, P. K., Tracey, K. J., & Metz, C. N. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802684 · Cited by 129 · see citing works
New therapeutic strategies for postoperative ileus
van Bree, S. H. W., Némethova, A., Cailotto, C., Gomez‐Pinilla, P. J., Matteoli, G., & Boeckxstaens, G. E. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.134 · Cited by 104 · see citing works
Rosas‐Ballina, M., Valdés‐Ferrer, S. I., Dancho, M. E., Ochani, M., Katz, D., Cheng, K. F., Olofsson, P. S., Chavan, S. S., Al‐Abed, Y., Tracey, K. J., et al. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.07.010 · Cited by 78 · see citing works
Kees, M. G., Pongratz, G., Kees, F., Schölmerich, J., & Straub, R. H. (2003) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.09.011 · Cited by 78 · see citing works
Neural control of the immune system
Sundman, E., & Olofsson, P. S. (2014) · Advances in Physiology Education · doi:10.1152/advan.00094.2013 · Cited by 74 · see citing works
Self-citationKlimaschewski, L. P., Kummer, W., & Heym, C. (1996) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19960901)35:1 · Cited by 55 · see citing works
Immune Cells Exploit a Neural Circuit to Enter the CNS
Tracey, K. J. (2012) · Cell · doi:10.1016/j.cell.2012.01.025 · Cited by 38 · see citing works
Treatment of chronic inflammatory diseases with implantable medical devices*
Zitnik, R. J. (2011) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.78.s1.05 · Cited by 17 · see citing works
Koopman, S. M. F. A. (2012) · Arthritis & Rheumatism · Cited by 14 · see citing works
A Stimulating Concept: Bioelectronic Medicine in Inflammatory Disease
Olofsson, P. S. (2014) · Bioelectronic Medicine · doi:10.15424/bioelectronmed.2014.00007 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Koopman, F. A., Chavan, S. S., Miljko, S., Grazio, S., Sokolovic, S., Schuurman, P. R., Mehta, A. D., Levine, Y. A., Faltys, M., Zitnik, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1605635113 · Cited by 1,024 · see citing works
Mechanisms and Therapeutic Relevance of Neuro-immune Communication
Chavan, S. S., Pavlov, V. A., & Tracey, K. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.008 · Cited by 661 · see citing works
Neural regulation of immunity: molecular mechanisms and clinical translation
Pavlov, V. A., & Tracey, K. J. (2017) · Nature Neuroscience · doi:10.1038/nn.4477 · Cited by 534 · see citing works
Molecular and functional neuroscience in immunity
Pavlov, V. A., Chavan, S. S., & Tracey, K. J. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053158 · Cited by 444 · see citing works
Self-citationCurrent Directions in the Auricular Vagus Nerve Stimulation I – A Physiological Perspective
Kaniušas, E., Kampusch, S., Tittgemeyer, M., Panetsos, F., Gines, R. F., Papa, M., Kiss, A., Podesser, B. K., Cassara, A. M., Tanghe, E., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00854 · Cited by 331 · see citing works
Pavlov, V. A., & Tracey, K. J. (2015) · Immunologic Research · doi:10.1007/s12026-015-8718-1 · Cited by 254 · see citing works
Komegae, E. N., Farmer, D., Brooks, V. L., McKinley, M. J., McAllen, R. M., & Martelli, D. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.06.005 · Cited by 146 · see citing works
Tanaka, S., Abe, C., Abbott, S. B. G., Zheng, S., Yamaoka, Y., Lipsey, J. E., Skrypnyk, N. I., Yao, J., Inoue, T., Nash, W., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021758118 · Cited by 129 · see citing works
Current Directions in the Auricular Vagus Nerve Stimulation II – An Engineering Perspective
Kaniušas, E., Kampusch, S., Tittgemeyer, M., Panetsos, F., Gines, R. F., Papa, M., Kiss, A., Podesser, B. K., Cassara, A. M., Tanghe, E., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00772 · Cited by 125 · see citing works
Neuroimmune Communication in Health and Disease
Reardon, C., Murray, K. M., & Lomax, A. E. (2018) · Physiological Reviews · doi:10.1152/physrev.00035.2017 · Cited by 116 · see citing works
Modulation of experimental arthritis by vagal sensory and central brain stimulation
Bassi, G. S., Dias, D. P. M., Franchin, M., Talbot, J., dos Reis, D. G., Menezes, G. B., Castania, J. A., Garcia‐Cairasco, N., Resstel, L. B. M., Salgado, H. C., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.04.003 · Cited by 99 · see citing works
Abdominal vagus nerve stimulation as a new therapeutic approach to prevent postoperative ileus
Stakenborg, N., Wolthuis, A. M., Gomez‐Pinilla, P. J., Farro, G., Giovangiulio, M. D., Bosmans, G., Labeeuw, E., Verhaegen, M., Depoortere, I., D’Hoore, A. J. L., et al. (2017) · Neurogastroenterology & Motility · doi:10.1111/nmo.13075 · Cited by 95 · see citing works
Caravaca, A. S., Gallina, A. L., Tarnawski, L., Shavva, V. S., Colas, R. A., Dalli, J., Malin, S., Hult, H., Arnardottir, H. H., & Olofsson, P. S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023285119 · Cited by 91 · see citing works
Pavlov, V. A., Chavan, S. S., & Tracey, K. J. (2019) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a034140 · Cited by 85 · see citing works
Implantable neurotechnologies: a review of integrated circuit neural amplifiers
Ng, K. A., Greenwald, E., Xu, Y. P., & Thakor, N. V. (2016) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-015-1431-3 · Cited by 83 · see citing works
Anatomical and clinical implications of vagal modulation of the spleen
Bassi, G. S., Kanashiro, A., Coimbra, N. C., Terrando, N., Maixner, W. D., & Ulloa, L. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.011 · Cited by 80 · see citing works
Chang, Y.-C., Cracchiolo, M., Ahmed, U., Mughrabi, I. T., Gabalski, A. H., Daytz, A. E., Rieth, L. W., Becker, L. B., Datta, T., Al‐Abed, Y., et al. (2020) · Brain stimulation · doi:10.1016/j.brs.2020.09.002 · Cited by 79 · see citing works
Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study
Marsal, S., Corominas, H., de Agustín, J. J., Pérez-García, C., Lasanta, M. L., Borrell, H., Reina, D., Sanmartí, R., Narváez, J., Franco‐Jarava, C., et al. (2021) · The Lancet Rheumatology · doi:10.1016/s2665-9913(20)30425-2 · Cited by 74 · see citing works
Comparison between the cervical and abdominal vagus nerves in mice, pigs, and humans
Stakenborg, N., Gomez‐Pinilla, P. J., Verlinden, T. J. M., Wolthuis, A. M., D’Hoore, A. J. L., Farré, R., Herijgers, P., Matteoli, G., & Boeckxstaens, G. E. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.13889 · Cited by 73 · see citing works
Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations
Noller, C. M., Levine, Y. A., Urakov, T. M., Aronson, J. P., & Nash, M. S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00911 · Cited by 70 · see citing works
An Effective Method for Acute Vagus Nerve Stimulation in Experimental Inflammation
Caravaca, A. S., Gallina, A. L., Tarnawski, L., Tracey, K. J., Pavlov, V. A., Levine, Y. A., & Olofsson, P. S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00877 · Cited by 68 · see citing works
Functional Circuitry of Neuro-Immune Communication in the Mesenteric Lymph Node and Spleen
Murray, K. M., Barboza, M., Rude, K. M., Brust‐Mascher, I., & Reardon, C. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.188 · Cited by 64 · see citing works
Tsaava, T., Datta-Chaudhuri, T., Addorisio, M. E., Battinelli, E., Silverman, H. A., Newman, J. E., Imperato, G. H., Bouton, C. E., Tracey, K. J., Chavan, S. S., et al. (2020) · Bioelectronic Medicine · doi:10.1186/s42234-020-00042-8 · Cited by 64 · see citing works
Anodal block permits directional vagus nerve stimulation
Ahmed, U., Chang, Y.-C., Cracchiolo, M., Lopez, M. F., Tomaio, J. N., Datta, T., Zanos, T. P., Rieth, L. W., Al‐Abed, Y., & Zanos, S. P. (2020) · Scientific Reports · doi:10.1038/s41598-020-66332-y · Cited by 59 · see citing works
Shin, H. C., Jo, B. G., Lee, C., Lee, K., & Namgung, U. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14368 · Cited by 56 · see citing works
Caravaca, A. S., Tsaava, T., Goldman, L., Silverman, H., Riggott, G., Chavan, S. S., Bouton, C., Tracey, K. J., Desimone, R., Boyden, E. S., et al. (2017) · Journal of Neural Engineering · doi:10.1088/1741-2552/aa7a42 · Cited by 57 · see citing works
Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex
Tarnawski, L., Reardon, C., Caravaca, A. S., Rosas‐Ballina, M., Tusche, M. W., Drake, A. R., Hudson, L., Hanes, W. M., Li, J. H., Parrish, W. R., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02648 · Cited by 57 · see citing works
Clinical studies and anti‐inflammatory mechanisms of treatments
French, J. A., Koepp, M. J., Naegelin, Y., Vigevano, F., Auvin, S., Rho, J. M., Rosenberg, E. C., Devinsky, O., Olofsson, P. S., & Dichter, M. A. (2017) · Epilepsia · doi:10.1111/epi.13779 · Cited by 54 · see citing works
Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis Survivors
Rana, M., Fei, Y., Son, M., Bella, A. L., Ochani, M., Levine, Y. A., Chiu, P. Y., Wang, P., Chavan, S. S., Volpe, B. T., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02032 · Cited by 50 · see citing works
Development and characterization of a chronic implant mouse model for vagus nerve stimulation
Mughrabi, I. T., Hickman, J. L., Jayaprakash, N., Thompson, D., Ahmed, U., Papadoyannis, E. S., Chang, Y.-C., Abbas, A., Datta, T., Chang, E. H., et al. (2021) · eLife · doi:10.7554/elife.61270 · Cited by 47 · see citing works
Nakamura, Y., Matsumoto, H., Wu, C.-H., Fukaya, D., Uni, R., Hirakawa, Y., Katagiri, M., Yamada, S., Ko, T., Nomura, S., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05051-2 · Cited by 46 · see citing works
Bremner, J. D., Gurel, N. Z., Jiao, Y., Wittbrodt, M. T., Levantsevych, O. M., Huang, M., Jung, H., Shandhi, M. H., Beckwith, J., Herring, I., et al. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100138 · Cited by 41 · see citing works
Falvey, A., Metz, C. N., Tracey, K. J., & Pavlov, V. A. (2021) · International Immunology · doi:10.1093/intimm/dxab068 · Cited by 40 · see citing works
Neural Prosthetics: A Review of Empirical vs. Systems Engineering Strategies
Loeb, G. E. (2018) · Applied Bionics and Biomechanics · doi:10.1155/2018/1435030 · Cited by 37 · see citing works
Meroni, E., Stakenborg, N., Gomez‐Pinilla, P. J., Stakenborg, M., Aguilera‐Lizarraga, J., Florens, M. V., Delfini, M., Simone, V. D., Hertogh, G. D., Goverse, G., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.694268 · Cited by 37 · see citing works
The shock tactics set to shake up immunology
Fox, D. (2017) · Nature · doi:10.1038/545020a · Cited by 36 · see citing works
Morris, J., Straube, A., Diener, H., Ahmed, F., Silver, N., Walker, S., Liebler, E. J., & Gaul, C. (2016) · The Journal of Headache and Pain · doi:10.1186/s10194-016-0633-x · Cited by 34 · see citing works
Efficacy of vagus nerve stimulation in gastrointestinal disorders: a systematic review
Veldman, F., Hawinkels, K., & Keszthelyi, D. (2025) · Gastroenterology report · doi:10.1093/gastro/goaf009 · Cited by 31 · see citing works
From Neuroimunomodulation to Bioelectronic Treatment of Rheumatoid Arthritis
Kanashiro, A., Bassi, G. S., Cunha, F. Q., & Ulloa, L. (2018) · Bioelectronics in Medicine · doi:10.2217/bem-2018-0001 · Cited by 30 · see citing works
Vagus Nerve Stimulation Reduces Indomethacin-Induced Small Bowel Inflammation
Caravaca, A. S., Levine, Y. A., Drake, A. R., Eberhardson, M., & Olofsson, P. S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.730407 · Cited by 28 · see citing works
Pathways of neuro-immune communication: past and present time, clinical application
Korneva, E. A. (2020) · Medical Immunology (Russia) · doi:10.15789/1563-0625-pon-1974 · Cited by 26 · see citing works
Flexible IrOx neural electrode for mouse vagus nerve stimulation
Sun, T., Tsaava, T., Peragine, J., Crosfield, C., Lopez, M. F., Modi, R., Sharma, R., Li, C., Sohal, H. S., Chang, E. H., et al. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.01.026 · Cited by 25 · see citing works
Impact of Non-Pharmacological Interventions on the Mechanisms of Atherosclerosis
Matei, D., Buculei, I., Luca, C. M., Corciovă, C., Andriţoi, D., Fuior, R., Iordan, D. A., & Onu, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169097 · Cited by 27 · see citing works
Immunity and the carotid body: implications for metabolic diseases
Conde, S. V., Sacramento, J. F., & Martins, F. O. (2020) · Bioelectronic Medicine · doi:10.1186/s42234-020-00061-5 · Cited by 24 · see citing works
Falvey, A., Palandira, S. P., Chavan, S. S., Brines, M. L., Dantzer, R., Tracey, K. J., & Pavlov, V. A. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.04.027 · Cited by 23 · see citing works
Falvey, A., Duprat, F., Simon, T., Hugues, S., Conde, S. V., Glaichenhaus, N., & Blancou, P. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02016-8 · Cited by 23 · see citing works
Zhou, Q., Yu, L., Yin, C., Zhang, Q., Wang, X., Kang, K., Shao, D., & Wang, Q. (2022) · Aging Clinical and Experimental Research · doi:10.1007/s40520-022-02177-x · Cited by 22 · see citing works
Harnessing the Inflammatory Reflex for the Treatment of Inflammation-Mediated DiseasesPreprint
Levine, Y. A., Faltys, M. A., & Chernoff, D. (2019) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a034330 · Cited by 22 · see citing works
He, Y., Zhao, C., Su, N., Yang, W., Yang, H., Yuan, C., Zhang, N., Hu, X., & Fu, Y. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114585 · Cited by 17 · see citing works
The brain–gut axis, inflammatory bowel disease and bioelectronic medicine
Eberhardson, M., Levine, Y. A., Tarnawski, L., & Olofsson, P. S. (2021) · International Immunology · doi:10.1093/intimm/dxab018 · Cited by 16 · see citing works
Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology
Sanchez, J. M. S., McNally, J. S., Cortez, M. M., Hemp, J., Pace, L., & Clardy, S. L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00787 · Cited by 13 · see citing works
Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats
Payne, S. C., Romas, E., Hyakumura, T., Muntz, F., & Fallon, J. B. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1012133 · Cited by 10 · see citing works
Cui, Y., Sun, J., Zhang, B., Guo, T., Zhang, S., Li, Z., Chen, Y., Su, M., Wu, D., Wu, J., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03132-8 · Cited by 11 · see citing works
Noninvasive Vagal Nerve Stimulation for Opioid Use Disorder
Bremner, J. D. (2023) · Annals of Depression and Anxiety · doi:10.26420/anndepressanxiety.2023.1117 · Cited by 7 · see citing works
Levine, Y. A., Simon, J., & Faltys, M. A. (2018) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2018.8513061 · Cited by 6 · see citing works
VNS for Treatment of Inflammatory Joint Diseases
Levine, Y. A., Simon, J., Koopman, F. A., Faltys, M. A., Zitnik, R. J., & Tak, P. P. (2017) · Springer eBooks · doi:10.1007/978-3-319-28612-9_2 · Cited by 5 · see citing works
Laryngeal Electromyography to Estimate A-Fiber Engagement by Vagal Stimuli in Mice
Abbas, A., Mughrabi, I. T., & Zanos, S. P. (2021) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/ner49283.2021.9441454 · Cited by 5 · see citing works
A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk
Bremner, J. D., Piccinelli, M., Garcia, E. V., Moncayo, V. M., Elon, L., Nye, J. A., David, C., Washington, B. P., Ortega, R. A., Desai, S., et al. (2023) · Medical Research Archives · doi:10.18103/mra.v11i4.3787 · Cited by 4 · see citing works
Deshmukh, A., Chen, R. C.-H., Chin, J., Knudsen, B. E., Trevathan, J. K., Shoffstall, A. J., & Ludwig, K. A. (2026) · Journal of Neural Engineering · doi:10.1088/1741-2552/ae52b7 · Cited by 4 · see citing works
Guo, Z., Chao, S.-Y., Kong, C., Xu, L., Cui, X. J., Yuan, X., Quan, Y.-C., Wang, M.-Y., Ma, Y.-L., Xiu-Jun, D. A. I., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68619-6 · Cited by 3 · see citing works
Vagus Nerve Stimulation and Regulation of Inflammation
Olofsson, P. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805353-9.00125-x · Cited by 3 · see citing works
Steiner, S. E., Choong, F. X., Antypas, H., Morado-Urbina, C. E., Schulz, A., Farinotti, A. B., Bas, D. B., Svensson, C. I., Richter‐Dahlfors, A., & Melican, K. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009553 · Cited by 3 · see citing works
Towards closed-loop neuromodulation: a wireless miniaturized neural implant SoC
Liu, W., Wang, P.-M., & Lo, Y. (2017) · Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE · doi:10.1117/12.2263566 · Cited by 3 · see citing works
Falvey, A., Palandira, S. P., Chavan, S. S., Brines, M. L., Tracey, K. J., & Pavlov, V. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.17.541191 · Cited by 3 · see citing works
Li, Q., Zhao, D., Zhang, S., Du, X., Ding, N., Xing, Z., Chu, X., & Xu, W. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1586632 · Cited by 2 · see citing works
Bioelectronic Medicines-A Novel Approach of Therapeutics in Current Epoch
Kumar, A., Ashawat, M. S., Pandit, V. R., & Kumar, P. (2024) · Current Pharmaceutical Design · doi:10.2174/0113816128326489240827100537 · Cited by 2 · see citing works
Autoimmune diseases: the immunological tightrope
Greener, M. (2022) · Prescriber · doi:10.1002/psb.2016 · Cited by 2 · see citing works
Tsaava, T., Datta-Chaudhuri, T., Addorisio, M. E., Battinelli, E., Silverman, H. A., Newman, J. E., Imperato, G. H., Bouton, C. E., Tracey, K. J., Chavan, S. S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.08.898890 · Cited by 2 · see citing works
Application of vagal nerve stimulation to post-traumatic stress disorder
Wittbrodt, M. T., Gurel, N. Z., Inan, O. T., Mehta, P. K., & Bremner, J. D. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-816996-4.00011-3 · Cited by 1 · see citing works
Progress on Direct Regulation of Systemic Immunity by the Central Nervous System
Tan, X., Zhang, J., Chen, W.-M., Chen, T., Cui, G., Liu, Z., & Hu, R. (2025) · World Neurosurgery · doi:10.1016/j.wneu.2025.123814 · Cited by 2 · see citing works
Chang, Y.-C., Ahmed, U., Jayaprakash, N., Mughrabi, I. T., Lin, Q., Wu, Y.-C., Gerber, M., Abbas, A., Daytz, A. E., Gabalski, A. H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.30.428827 · Cited by 1 · see citing works
Transcutaneous Vagal Nerve Stimulation in Trauma Spectrum Psychiatric Disorders
Bremner, J. D., Wittbrodt, M. T., Gurel, N. Z., Shandhi, M. M. H., Gazi, A. H., Park, J., & Inan, O. T. (2023) · Neuromethods · doi:10.1007/978-1-0716-3465-3_8
Chang, A. (2024) · Cambridge University Press eBooks · doi:10.1017/9781108917339.003
MODERN VIEWS ABOUT THE IMMUNO-INDUCED PROCESS IN MUSCLES DURING PHYSICAL ACTIVITY
Muzhenya, D. V., Lysenkov, S. P., Рамазановна, Т. А., & Shumilov, D. S. (2024) · Scientific Notes of V I Vernadsky Crimean Federal University Biology Chemistry · doi:10.29039/2413-1725-2024-10-3-128-146
Mintser, O. P., Заліський, В. М., & Бабінцева, Л. Ю. (2025) · Medical Informatics and Engineering · doi:10.11603/mie.1996-1960.2024.3-4.15461
Ran, R., Zhao, Y., Zhao, J., Hu, L., Zhang, S., Gong, C., Guo, C., Shan, M., Wang, R., Xie, Q. M., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9107953/v1
Guo, Q., Holíček, P., Tarnawski, L., & Olofsson, P. S. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-026-01418-y
Nahm, W. J., Kim, K., NamGung, E., Koo, J., Han, Y., & Falanga, V. (2026) · Experimental Dermatology · doi:10.1111/exd.70297
Mirandette, K. S., Sahasrabudhe, A., Slowikowski, M., Caldwell, J. H., Anikeeva, P., Weir, R. F. F., & Fontaine, A. K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.10.731452
Bremner, J. D., Gazi, A. H., Gurel, N. Z., Lambert, T. P., Wittbrodt, M. T., Welsh, J. W., Pearce, B. D., Vaccarino, V., Shah, A. J., & Inan, O. T. (2026) · Stress · doi:10.1080/10253890.2026.2726826
- Authors
- Olofsson, P. S., Levine, Y. A., Caravaca, A., Chavan, S. S., Pavlov, V. A., Faltys, M., & Tracey, K. J.
- Affiliations
- Feinstein Institute for Medical Research (US)
- Corresponding author
- Olofsson, Peder S.
- Levine, Yaakov A.
- ORCID
- Venue
- Bioelectronic Medicine
- Published
- 2015-05-13
- Volume
- 2
- Issue
- 1
- Pages
- 37-42
- ISSN
- 2332-8886 (ISSN-L)
- OpenAlex
- W2897292905
- Cited by
- 81
- References
- 44
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 3 · 2015: 1
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- creativecommons.org/licenses/by/4.0 (tdm)
- Locations
- Bioelectronic Medicine (publishedVersion, cc-by-nc-nd)
- Funders
- Svenska Läkaresällskapet
- National Institute of General Medical Sciences (R01GM089807)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- cervical vagus nerve, cholinergic anti-inflammatory pathway, TNF-α, endotoxemia, alpha7 nicotinic acetylcholine receptor, macrophages, cytokine inhibition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
