#CRPS Bugle 10 July

Welcome to the latest CRPS BugleCRPS Bugle

In this study it was found that in the early stages of CRPS the blister fluid contained pro-inflammatory cytokines that at six months were similar to non-CRPS patients. This supports the findings of a systematic review of the literature undertaken earlier this year (see below) that identified different inflammatory profiles according to whether the state was acute or chronic. This data steers our understanding of the inflammatory pain mechanisms in CRPS and consequently guides the treatment and training strategies that must be appropriate for the individual and the stage of the condition. RS – Specialist Pain Physio Clinics, London

Pain. 2013 Jun 27. pii: S0304-3959(13)00360-6

Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months.

Lenz M, Uçeyler N, Frettlöh J, Höffken O, Krumova EK, Lissek S, Reinersmann A, Sommer C, Stude P, Waaga-Gasser AM, Tegenthoff M, Maier C.


There is evidence that inflammatory processes are involved at least in the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and anti-inflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper limb pain of other origin (non-CRPS) in the early stage (< 1 year) and after six months of pain treatment.


Blister fluid was collected from the affected and contralateral non-affected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β).


We found bilaterally increased pro-inflammatory TNF-α and MIP-1β and decreased anti-inflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After six months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences.


Blister fluid of CRPS patients showed a bilateral pro-inflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after six months of analgesic treatment and were not related to treatment outcome.


Neurology. 2013 Jan 1;80(1):106-17. – Full article here

Inflammation in complex regional pain syndrome: a systematic review and meta-analysis.

Parkitny L, McAuley JH, Di Pietro F, Stanton TR, O’Connell NE, Marinus J, van Hilten JJ, Moseley GL.


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.


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.


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.


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.


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