Complex regional pain syndrome: a focus on the autonomic nervous system

  • Lone F. Knudsen
  • Astrid J. Terkelsen
  • Peter D. Drummond
  • Frank BirkleinEmail author
Review Article



Although autonomic features are part of the diagnostic criteria for complex regional pain syndrome (CRPS), the role of the autonomic nervous system in CRPS pathophysiology has been downplayed in recent years. The purpose of this review is to redress this imbalance.


We focus in this review on the contribution of the autonomic nervous system to CRPS pathophysiology. In particular, we discuss regional sympathetic and systemic autonomic disturbances in CRPS and the mechanisms which may underlie them, and consider links between these mechanisms, immune disturbances and pain.


The focused literature research revealed that immune reactions, alterations in receptor populations (e.g., upregulation of adrenoceptors and reduced cutaneous nerve fiber density) and central changes in autonomic drive seem to contribute to regional and systemic disturbances in sympathetic activity and to sympathetically maintained pain in CRPS.


We conclude that alterations in the sympathetic nervous system contribute to CRPS pathology. Understanding these alterations may be an important step towards providing appropriate treatments for CRPS.


Complex regional pain syndrome Sympathetic nervous system Central disturbances in autonomic activity Immune system 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Danish National Rehabilitation Centre for Neuromuscular DiseasesAarhusDenmark
  2. 2.Danish Pain Research Center, Department of NeurologyAarhus University HospitalAarhusDenmark
  3. 3.College of ScienceHealth, Engineering and Education, Murdoch UniversityPerthAustralia
  4. 4.Department of NeurologyUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany

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