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BMC Neurology
Published in: BMC Neurology 1/2022

Open Access 01-12-2022 | Complex Regional Pain Syndrome | Research

Post-fracture serum cytokine levels are not associated with a later diagnosis of complex regional pain syndrome: a case-control study nested in a prospective cohort study

Authors: Luke Parkitny, James H McAuley, Robert D. Herbert, Flavia Di Pietro, Aidan G Cashin, Michael C Ferraro, G. Lorimer Moseley

Published in: BMC Neurology | Issue 1/2022

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Abstract

Background

Complex Regional Pain Syndrome (CRPS) is a disabling pain disorder that is most common after a distal limb fracture. While the acute systemic immune response to the injury is thought to play a role in the development of CRPS, this hypothesis has never been tested directly. Thus, we evaluated whether elevated levels of circulating pro-inflammatory cytokines early after a fracture were associated with the development of CRPS.

Methods

We conducted a case-control study nested within a prospective cohort study. Individuals with wrist and/or hand fractures were recruited from specialist hand units. Baseline clinical data were obtained from participants within 28 days of fracture. CRPS status was determined 16 weeks after the fracture using a two-stage diagnostic process. Cytokine assays were obtained from all cases (defined using the Budapest criteria) and a random sample of those who did not have CRPS at 16 weeks. We calculated odds ratios with 95% confidence intervals to determine the risk of CRPS associated with the expression of each of 25 cytokines.

Results

Baseline data were collected for 702 consenting participants, of whom 535 provided blood samples. Follow-up at 16 weeks was 97.2%. 15 (2.2% of the cohort) met the Budapest CRPS criteria and 69 (including those who met the Budapest criteria; 9.8%) met the International Association for the Study of Pain (IASP) CRPS criteria. In all of the primary analyses (using Budapest criteria) and 49/50 secondary analyses (using IASP criteria), 95% confidence intervals for the association between cytokine levels and the risk of subsequently developing CRPS included the null value (OR = 1). However, the confidence intervals were wide.

Conclusion

There was no evidence that early post-injury expression of systemic cytokines was associated with a CRPS diagnosis 16 weeks after injury. This study does not provide support for the hypothesis that innate immune activation has a determinative role in the development of CRPS.
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Metadata
Title
Post-fracture serum cytokine levels are not associated with a later diagnosis of complex regional pain syndrome: a case-control study nested in a prospective cohort study
Authors
Luke Parkitny
James H McAuley
Robert D. Herbert
Flavia Di Pietro
Aidan G Cashin
Michael C Ferraro
G. Lorimer Moseley
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-022-02910-z

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