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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2024

Open Access 01-12-2024 | Complex Regional Pain Syndrome | Research

Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome

Authors: Beate Hartmannsberger, Sabrina Scriba, Carolina Guidolin, Juliane Becker, Katharina Mehling, Kathrin Doppler, Claudia Sommer, Heike L. Rittner

Published in: Journal of Neuroinflammation | Issue 1/2024

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Abstract

Background

Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.

Methods

We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.

Results

Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.

Conclusions

Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.
Appendix
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Metadata
Title
Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome
Authors
Beate Hartmannsberger
Sabrina Scriba
Carolina Guidolin
Juliane Becker
Katharina Mehling
Kathrin Doppler
Claudia Sommer
Heike L. Rittner
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02969-6

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