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      Neuropathic pain: an updated grading system for research and clinical practice

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          Abstract

          The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

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          Most cited references 33

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          Central sensitization: implications for the diagnosis and treatment of pain.

          Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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            Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

            New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis.
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              Neuropathic pain: redefinition and a grading system for clinical and research purposes.

              Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.
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                Author and article information

                Journal
                Pain
                Pain
                JPAIN
                Pain
                JOP
                Pain
                Wolters Kluwer (Philadelphia, PA )
                0304-3959
                1872-6623
                13 January 2016
                August 2016
                : 157
                : 8
                : 1599-1606
                Affiliations
                [a ]Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
                [b ]Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA
                [c ]Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
                [d ]Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
                [e ]Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom
                [f ]INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France
                [g ]Université Versailles-Saint-Quentin, Versailles, France
                [h ]Department of Neurology and Psychiatry, Sapienza University, Rome, Italy
                [i ]Autonomic and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
                [j ]Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway
                [k ]Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [l ]Pain Research Institute, Neuroscience Research Centre, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
                [m ]Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
                [n ]Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, United Kingdom
                [o ]Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom
                [p ]Neuroscience Technologies, Ltd, Barcelona, Spain
                [q ]Ninewells Hospital and Medical School, Division of Population Health Sciences, School of Medicine, University of Dundee, Dundee, Scotland
                [r ]Chair of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany
                [s ]Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
                Author notes
                [* ]Corresponding author. Address: Danish Pain Research Center, Aarhus University, Aarhus University Hospital, Norrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. Tel.: +45 7846 4230; fax: +45 7846 3269. E-mail address: finnerup@ 123456clin.au.dk (N. B. Finnerup).
                PAIN-D-14-14267 00007
                10.1097/j.pain.0000000000000492
                4949003
                27115670
                © 2016 International Association for the Study of Pain

                This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Anesthesiology & Pain management

                grading, neuropathic pain, definition, possible, probable, definite

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