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) TNFa, bradykinin, sIL-1RI, IL-1Ra, IL-2, sIL-2Ra, IL-4, IL-7, interferong, monocyte chemoattractant protein-1 (MCP-1), and sRAGE (soluble receptor for advanced glycation end products) in blood; 2) IL-1Ra, MCP-1, MIP-1b, and IL-6 in blister fluid; and 3) IL-1b 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 5 confidence interval; CGRP 5 calcitonin gene-relaxed peptide; CRPS 5 complex regional pain syndrome; ET-1 5 endothelin-1; IL 5 interleukin; IP-10 5 interferon-inducible protein-10; MCP-1 5 monocyte chemoattractant protein-1; NPY 5 neuropeptide Y; PGE2 5 prostaglandin E2; SP 5 substance P; sTNF-R 5 soluble tumor necrosis factor receptor; TNF 5 tumor necrosis factor.Complex regional pain syndrome (CRPS) is characterized by severe pain, allodynia, hyperalgesia, and motor and autonomic signs and symptoms.1 Although the precise etiology of CRPS is unknown, persistent inflammatory activity has been demonstrated in a number of methodologically diverse studies.2-6 Although narrative reviews have attempted to synthesize these results, no systematic review including a rigorous quality assessment of original studies has been conducted. As such, no definitive conclusions can be drawn about the presence of inflammatory activity in CRPS, which limits the identification of potential targets for therapy. Therefore, we conducted a systematic review and meta-analysis of the literature. We aimed firstly to determine whether, in adults, CRPS is associated with a...