Key Points
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Complex regional pain syndromes (CRPS) are multifactorial disorders; the heterogeneity of clinical signs and symptoms reflects different underlying pathophysiological mechanisms
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Peripheral mechanisms of CRPS include inflammation, peripheral sensitization and sympatho-afferent coupling
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Central mechanisms include neuroplastic changes, such as cortical reorganization, afferent–efferent feedback conflicts and central autonomic dysregulation
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Individual variation in pathophysiological mechanisms offer the opportunity for several mechanism-based treatment options
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To date, only a few clinical trials have assessed the long-term efficacy of therapies specifically for CRPS
Abstract
Complex regional pain syndromes (CRPS) are multifactorial disorders with complex aetiology and pathogenesis. Management of CRPS is challenging, partly because of a lack of clinical data regarding the efficacy of the various therapies, and partly because successful treatment of CRPS requires a multidisciplinary, patient-tailored approach. The pain in CRPS is often described as typical 'burning' neuropathic pain, and is accompanied by a variety of sensory, motor and autonomic signs and symptoms. Because research into therapies specifically in CRPS has been scarce, treatment for these syndromes has been largely based on therapeutic strategies adapted from neuropathic pain states; however, increased understanding of the pathogenesis of CRPS has provided the opportunity to develop mechanism-based treatments. The interactions between the multiple pathophysiological mechanisms that contribute to the development, progression and maintenance of CRPS remain poorly understood. This Review describes the challenges in linking the current theories and knowledge of pathophysiological mechanisms to the mode of actions of the different treatment approaches. We discuss the current treatment strategies for CRPS, including pharmacotherapy, sympathetic ganglion block interventions, psychological support, physiotherapy and occupational therapy, and establish the concept of mechanism-based treatment for CRPS.
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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.
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J.G. has received honoraria from Grünenthal and Pfizer. A.B. has received honoraria from Astellas, Allergan, Bayer, Boehringer-Ingelheim, Grünenthal and Pfizer and participated in the advisory boards of Astellas, Boehringer-Ingelheim, Genzyme, and Grünenthal. R.B. has received grant/research support from Pfizer, Genzyme and Grünenthal. He is a member of the IMI EuroPain collaboration, in which the following industry members are represented: Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Esteve, Grünenthal, Pfizer, UCB-Pharma and Sanofi Aventis. He has received honoraria as a speaker from Astellas, Bayer-Schering, Boehringer Ingelheim, Desitin, Eisai, Eli Lilly, Genzyme, Grünenthal, Medtronic, Mundipharma, MSD, Pfizer, Sanofi Pasteur and Teva Pharma. He is also a consultant for Abbvie, Allergan, Astellas, AstraZeneca, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Eli Lilly, Genzyme, Grünenthal, Medtronic, Merck, Mundipharma, Novartis, Pfizer and Sanofi Pasteur.
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Gierthmühlen, J., Binder, A. & Baron, R. Mechanism-based treatment in complex regional pain syndromes. Nat Rev Neurol 10, 518–528 (2014). https://doi.org/10.1038/nrneurol.2014.140
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DOI: https://doi.org/10.1038/nrneurol.2014.140
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