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
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Date
2022
Authors
Parkitny, L.
McAuley, J.H.
Herbert, R.D.
Di Pietro, F.
Cashin, A.G.
Ferraro, M.C.
Moseley, G.L.
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BMC Neurology, 2022; 22(1, article no. 385):1-11
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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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Data source: Electronic supplementary material, https://doi.org/10.1186/s12883-022-02910-z
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Copyright 2022 The author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. (http://creativecommons.org/licenses/by/4.0/)