Molecular Medicine

, Volume 17, Issue 9–10, pp 937–948 | Cite as

Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis

  • Frieda A. Koopman
  • Susanne P. Stoof
  • Rainer H. Straub
  • Marjolein A. van Maanen
  • Margriet J. Vervoordeldonk
  • Paul P. Tak
Review Article


The immunomodulatory effect of the autonomic nervous system has raised considerable interest over the last decades. Studying the influence on the immune system and the role in inflammation of the sympathetic as well as the parasympathetic nervous system not only will increase our understanding of the mechanism of disease, but also could lead to the identification of potential new therapeutic targets for chronic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). An imbalanced autonomic nervous system, with a reduced parasympathetic and increased sympathetic tone, has been a consistent finding in RA patients. Studies in animal models of arthritis have shown that influencing the sympathetic (via α- and β-adrenergic receptors) and the parasympathetic (via the nicotinic acetylcholine receptor α7nAChR or by electrically stimulating the vagus nerve) nervous system can have a beneficial effect on inflammation markers and arthritis. The immunosuppressive effect of the parasympathetic nervous system appears less ambiguous than the immunomodulatory effect of the sympathetic nervous system, where activation can lead to increased or decreased inflammation depending on timing, doses and kind of adrenergic agent used. In this review we will discuss the current knowledge of the role of both the sympathetic (SNS) and parasympathetic nervous system (PNS) in inflammation with a special focus on the role in RA. In addition, potential antirheumatic strategies that could be developed by targeting these autonomic pathways are discussed.



Supported by Dutch Arthritis Association grant NR 09-1-307. In addition, the authors would like to thank Beatrijs M Lodde for editorial assistance.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Frieda A. Koopman
    • 1
  • Susanne P. Stoof
    • 1
    • 2
  • Rainer H. Straub
    • 3
  • Marjolein A. van Maanen
    • 1
  • Margriet J. Vervoordeldonk
    • 1
    • 2
  • Paul P. Tak
    • 1
  1. 1.Division of Clinical Immunology and Rheumatology, F4-105Academic Medical Center/University of AmsterdamAmsterdamThe Netherlands
  2. 2.Arthrogen BVAmsterdamThe Netherlands
  3. 3.Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine IUniversity Hospital RegensburgRegensburgGermany

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