title: Inflammation in complex regional pain syndrome: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroscience Research Australia, University of New South Wales, Sydney, Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Parkitny
authors.forename: James H
authors.initials: JH
authors.lastname: McAuley
authors.forename: Flavia
authors.initials: F
authors.lastname: Di Pietro
authors.forename: Tasha R
authors.initials: TR
authors.lastname: Stanton
authors.forename: Neil E
authors.initials: NE
authors.lastname: O'Connell
authors.forename: Johan
authors.initials: J
authors.lastname: Marinus
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.forename: G Lorimer
authors.initials: GL
authors.lastname: Moseley
mesh_terms: D059787:Acute Pain / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D001768:Blister / Q000378:metabolism; D059350:Chronic Pain / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D020918:Complex Regional Pain Syndromes / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators