Vagal afferent activation suppresses systemic inflammation via the splanchnic anti-inflammatory pathway

Evilin Naname Komegae, David George Stephen Farmer, Virginia Leah Brooks, Michael Joseph McKinley, Robin Michael McAllen, Davide Martelli

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Electrical stimulation of the vagus nerve (VNS) is a novel strategy used to treat inflammatory conditions. Therapeutic VNS activates both efferent and afferent fibers; however, the effects attributable to vagal afferent stimulation are unclear. Here, we tested if selective activation of afferent fibers in the abdominal vagus suppresses systemic inflammation. In urethane-anesthetized rats challenged with lipopolysaccharide (LPS, 60 µg/kg, i.v.), abdominal afferent VNS (2 Hz for 20 min) reduced plasma tumor necrosis factor alpha (TNF) levels 90 min later by 88% compared with unmanipulated animals. Pre-cutting the cervical vagi blocked this anti-inflammatory action. Interestingly, the surgical procedure to expose and prepare the abdominal vagus for afferent stimulation (‘vagal manipulation’) also had an anti-inflammatory action. Levels of the anti-inflammatory cytokine IL-10 were inversely related to those of TNF. Prior bilateral section of the splanchnic sympathetic nerves reversed the anti-inflammatory actions of afferent VNS and vagal manipulation. Sympathetic efferent activity in the splanchnic nerve was shown to respond reflexly to abdominal vagal afferent stimulation. These data demonstrate that experimentally activating abdominal vagal afferent fibers suppresses systemic inflammation, and that the efferent neural pathway for this action is in the splanchnic sympathetic nerves.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
JournalBrain, Behavior, and Immunity
StatePublished - Oct 2018


  • Endotoxemia
  • Greater splanchnic nerve
  • Inflammation
  • Interleukin 10 (IL-10)
  • Lipopolysaccharide (LPS)
  • Splanchnic anti-inflammatory pathway
  • Sympathetic nervous system
  • Tumor necrosis factor α (TNF)
  • Vagus nerve
  • Vagus nerve stimulation

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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