Abstract
Acute Complex Regional Pain Syndrome (CRPS) is associated with signs of inflammation
such as increased skin temperature, oedema, skin colour changes and pain. Pro-inflammatory
cytokines (tumour necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-1beta, IL-6)
are up-regulated, whereas anti-inflammatory cytokines (IL-4, IL-10) are diminished.
Adaptive immunity seems to be involved in CRPS pathophysiology as many patients have
autoantibodies directed against β2 adrenergic and muscarinic-2 receptors. In an animal tibial fracture model changes
in the innate immune response such as up-regulation of keratinocytes are also found.
Additionally, CRPS is accompanied by increased neurogenic inflammation which depends
mainly on neuropeptides such as CGRP and Substance P.
Besides inflammatory signs, sympathetic nervous system involvement in CRPS results
in cool skin, increased sweating and sympathetically-maintained pain. The norepinephrine
level is lower in the CRPS-affected than contralateral limb, but sympathetic sprouting
and up-regulation of alpha-adrenoceptors may result in an adrenergic supersensitivity.
The sympathetic nervous system and inflammation interact: norepinephrine influences
the immune system and the production of cytokines. There is substantial evidence that
this interaction contributes to the pathophysiology and clinical presentation of CRPS,
but this interaction is not straightforward. How inflammation in CRPS might be exaggerated
by sympathetic transmitters requires further elucidation.
Keywords
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Article info
Publication history
Published online: January 13, 2014
Accepted:
December 11,
2013
Received:
October 29,
2013
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
