Modulation of experimental arthritis by vagal sensory and central brain stimulation

Gabriel Shimizu Bassi, Daniel Penteado Martins Dias, Marcelo Franchin, Jhimmy Talbot, Daniel Gustavo Reis, Gustavo Batista Menezes, Jaci Airton Castania, Norberto Garcia-Cairasco, Leonardo Barbosa Moraes Resstel, Helio Cesar Salgado, Fernando Queiróz Cunha, Thiago Mattar Cunha, Luis Ulloa, Alexandre Kanashiro

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel “afferent” pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations.

Original languageEnglish (US)
Pages (from-to)330-343
Number of pages14
JournalBrain, Behavior, and Immunity
StatePublished - Aug 2017

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


  • Arthritis
  • Neuroimmune interactions
  • Neuroimmunomodulation
  • Neutrophil migration
  • Sympathetic nervous system
  • Vagus nerve

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