Neuroimmune alterations in the complex regional pain syndrome

Department of Anaesthesiology, Erasmus University Medical Centre Rotterdam, Dijkzigt Hospital, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
European Journal of Pharmacology (Impact Factor: 2.68). 11/2001; 429(1-3):101-113. DOI: 10.1016/S0014-2999(01)01310-3
Source: PubMed

ABSTRACT This review focuses on some clinical aspects of the complex regional pain syndrome, such as oedema, local temperature changes and chronic pain, as a result of supposed neurogenic inflammation. Involvement of the immune system could imply the subsequent release of neuropeptides, pro-inflammatory cytokines and eicosanoids, which in turn leads to a complex cross-talk of primary and secondary generated mediators of inflammation. The development and application of drugs that act through selective receptor antagonism or enzymatic synthesis inhibition to prevent further stimulation of this cascade that could inevitably lead to chronicity of this disease are extensively discussed.

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    • "Nerve growth factor is one of the cytokines activated by the substance P, and its activity leads to nociceptive sensitization, enhanced osteopenia with increased cytokine content (Sabsovich et al., 2008). Tumor necrosis factor alpha is another pro-inflammatory cytokine postulated to play a role in the development of CRPS changes after trauma and its expression is increased in CRPS patients (Huygen et al., 2001). Although the increased level of the tumor necrosis factor is an important mediator of regional nociceptive sensitization, it does not contribute to the enhanced bone loss (Sabsovich et al., 2008). "
    Osteoporosis, 02/2012; , ISBN: 978-953-51-0026-3
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    • "evidence based. The patient-dependent choice of either physical therapy, pharmaceutical intervention, or unconventional alternative medicine is still a matter of debate [8] [11]. Targeted treatment with anti-TNF (Infliximab) seems, however, to be successful in patients with confirmed signs of inflammation [12]. "
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    ABSTRACT: Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNFα compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1β, IL-1RA, IL-6, IL-8, and TNF-α; (2) Th1/Th2 distinguishing cytokines IFN-γ, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-α, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-α, IL-12p40/p70, MCP-1, and MIP-1β were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-α simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85, P < .001 for IL-6 and r = 0.88, P < .001 for TNF-α). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines.
    Mediators of Inflammation 02/2006; 2006(1):28398. DOI:10.1155/MI/2006/28398 · 3.24 Impact Factor
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    • "Furthermore , an extension of the tested pallet of cytokines should be considered in order to unravel the contribution of specific cytokines (pro-and anti-inflammatory cytokines, Th1/Th2 cell-derived cytokines, chemokines) during the whole course of the disease. More insight in the timerelated contribution of specific cytokines will enable the selective use of immunosuppressives [7] [18] or the specific development of disease-modifying agents. "
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    ABSTRACT: The aim of this paper is to determine the involvement of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in intermediate CRPS 1 as locally formed mediators of inflammation. In this study, 25 patients with proven CRPS 1 (Bruehl criteria) were included. All patients participated in one of our earlier studies during the acute stage of their disease. After the disease developed into an intermediate stage, both the disease activity and the profile of inflammatory mediators were reevaluated. Disease activity and impairment were determined by means of a visual analogue scale, the McGill Pain Questionnaire, the difference in volume and temperature between the involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Suction blisters were made on the involved and uninvolved extremities for measurement of IL-6 and TNF-alpha. A significant improvement in signs and symptoms of impairment was found. However, the levels of IL-6 and TNF-alpha in blister fluid in the involved extremity versus uninvolved extremity were still significantly raised. Although signs and symptoms are significantly improved, proinflammatory cytokines are still increased in CRPS 1 affected extremities during the intermediate stage of the disease. This indicates that the initiation and sustained development of the disease are only partially affected by proinflammatory cytokines. Follow-up in the chronic stage is necessary to draw more definite conclusions about the existence of a supposed relation between clinical signs and symptoms and the level of proinflammatory cytokines.
    Mediators of Inflammation 01/2006; 2005(6):366-72. DOI:10.1155/MI.2005.366 · 3.24 Impact Factor
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