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January 01, 2013; 80 (1) Views & Reviews

Inflammation in complex regional pain syndrome

A systematic review and meta-analysis

Luke Parkitny, James H. McAuley, Flavia Di Pietro, Tasha R. Stanton, Neil E. O’Connell, Johan Marinus, Jacobus J. van Hilten, G. Lorimer Moseley
First published December 24, 2012, DOI: https://doi.org/10.1212/WNL.0b013e31827b1aa1
Luke Parkitny
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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James H. McAuley
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Flavia Di Pietro
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Tasha R. Stanton
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Neil E. O’Connell
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Johan Marinus
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Jacobus J. van Hilten
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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G. Lorimer Moseley
From Neuroscience Research Australia (L.P., J.H.M., F.D.P., T.R.S.) and Prince of Wales Clinical School (L.P., F.D.P.), University of New South Wales, Sydney; Sansom Institute for Health Research (T.R.S., G.L.M.), University of South Australia, Adelaide, Australia; Centre for Research in Rehabilitation (N.E.O), Brunel University, Uxbridge, UK; Department of Neurology (J.M., J.J.v.H.), Leiden University Medical Center, Leiden, the Netherlands.
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Citation
Inflammation in complex regional pain syndrome
A systematic review and meta-analysis
Luke Parkitny, James H. McAuley, Flavia Di Pietro, Tasha R. Stanton, Neil E. O’Connell, Johan Marinus, Jacobus J. van Hilten, G. Lorimer Moseley
Neurology Jan 2013, 80 (1) 106-117; DOI: 10.1212/WNL.0b013e31827b1aa1

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ABSTRACT

Objectives: We conducted a systematic review of the literature with meta-analysis to determine whether complex regional pain syndrome (CRPS) is associated with a specific inflammatory profile and whether this is dependent on the duration of the condition.

Methods: Comprehensive searches of the literature using MEDLINE, Embase, Scopus, Web of Science, and reference lists from published reviews identified articles that measured inflammatory factors in CRPS. Two independent investigators screened titles and abstracts, and performed data extraction and risk of bias assessments. Studies were subgrouped by medium (blood, blister fluid, and CSF) and duration (acute and chronic CRPS). Where possible, meta-analyses of inflammatory factor concentrations were performed and pooled effect sizes were calculated using random-effects models.

Results: Twenty-two studies were included in the systematic review and 15 in the meta-analysis. In acute CRPS, the concentrations of interleukin (IL)-8 and soluble tumor necrosis factor receptors I (sTNF-RI) and II (sTNF-RII) were significantly increased in blood. In chronic CRPS, significant increases were found in 1) TNFα, bradykinin, sIL-1RI, IL-1Ra, IL-2, sIL-2Ra, IL-4, IL-7, interferon-γ, monocyte chemoattractant protein-1 (MCP-1), and sRAGE (soluble receptor for advanced glycation end products) in blood; 2) IL-1Ra, MCP-1, MIP-1β, and IL-6 in blister fluid; and 3) IL-1β and IL-6 in CSF. Chronic CRPS was also associated with significantly decreased 1) substance P, sE-selectin, sL-selectin, sP-selectin, and sGP130 in blood; and 2) soluble intercellular adhesion molecule-1 (sICAM-1) in CSF. Most studies failed to meet 3 or more of our quality criteria.

Conclusion: CRPS is associated with the presence of a proinflammatory state in the blood, blister fluid, and CSF. Different inflammatory profiles were found for acute and chronic cases.

GLOSSARY

CI=
confidence interval;
CGRP=
calcitonin gene-relaxed peptide;
CRPS=
complex regional pain syndrome;
ET-1=
endothelin-1;
IL=
interleukin;
IP-10=
interferon-inducible protein-10;
MCP-1=
monocyte chemoattractant protein-1;
NPY=
neuropeptide Y;
PGE2=
prostaglandin E2;
SP=
substance P;
sTNF-R=
soluble tumor necrosis factor receptor;
TNF=
tumor necrosis factor

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received May 16, 2012.
  • Accepted August 9, 2012.
  • © 2012 American Academy of Neurology
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