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Role of peripheral nerve fibres in acute and chronic inflammation in arthritis

Nature Reviews Rheumatology volume 9, pages 117–126 (2013)Cite this article

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Abstract

The peripheral nervous system takes an active part in inflammatory processes by regulating effector cell function and reallocation of energy to the immune system. During acute inflammation, rapid neuronal reorganization and change of activity takes place. The hallmarks of this process are an increase in systemic sympathetic activity, a decrease in systemic parasympathetic activity and loss of sympathetic nerve fibres from sites of inflammation concomitant with increased innervation with sensory nerve fibres and increased sensory nerve fibre activity. On a systemic level, the increase in sympathetic activity (and decrease in parasympathetic activity) is necessary to provide enough energy to nourish the activated immune system. In locally inflamed tissue, the decrease in sympathetic nerve fibre density results in reduced anti-inflammatory signalling and, together with neuropeptides released from sensory nerve fibres, promotes local inflammation. In acute inflammation, this 'inflammatory configuration' of the peripheral nervous system favours the rapid clearance of antigenic threats. However, in chronic autoimmune inflammation, these changes of the peripheral nervous system lead to an unfavourable situation with ongoing energy reallocation and continuous local destruction. As an example of a chronic inflammatory condition, we discuss evidence for neuroimmune regulation in autoimmune arthritis with a focus on the sympathetic nervous system.

Key Points

  • The peripheral nervous system has an active and important role in every inflammatory process; for example, by directly influencing immune effector cells and by regulating energy supply to the immune system

  • The sympathetic, parasympathetic and sensory branches of the peripheral nervous system can have proinflammatory or anti-inflammatory effects, or both, depending on their site of action, nerve fibre density and timing

  • During inflammation, neuronal reorganization enables the establishment of a 'proinflammatory neuronal configuration' locally (at the site of inflammation and in lymphoid organs) and systemically (at the whole-body level)

  • This neuronal configuration is favourable for the rapid clearance of antigen in acute inflammatory processes, but is unfavourable in chronic inflammation and leads to continuous loss of bodily energy, water retention and support of ongoing tissue destruction

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Figure 1: The components of a polymodal nociceptor.
Figure 2: Restructuring of neuronal innervation during inflammation leading to loss of sympathetic nerve fibres and sprouting of sensory nerve fibres in inflamed tissue.
Figure 3: Timescale of inflammation.
Figure 4: Current model of sympathetic neuroimmune regulation in collagen-type II induced arthritis.

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Acknowledgements

Over many years, the authors' research has been supported by the University Hospital Regensburg, the Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG), in particular their funding of DFG Research Unit FOR696.

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  1. Department of Internal Medicine I, Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg, Regensburg, 93042, Germany

    Georg Pongratz & Rainer H. Straub

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Pongratz, G., Straub, R. Role of peripheral nerve fibres in acute and chronic inflammation in arthritis. Nat Rev Rheumatol 9, 117–126 (2013). https://doi.org/10.1038/nrrheum.2012.181

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