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Pain. 2015 Nov;156(11):2337-53. doi: 10.1097/j.pain.0000000000000335.

Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations.

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aDivision of Population Health Sciences, University of Dundee, Dundee, Scotland, United Kingdom bBrain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa cINSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt, France dUniversité Versailles Saint-Quentin, Versailles, France eDivision of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany fdeCODE Genetics/Amgen, Reykjavík, Iceland gNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom hAcademic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom iThe Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada jDepartment of Neurology, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, USA kZentrum für Anästhesiologie, Intensivmedizin, Schmerztherapie und Palliativmedizin, Benedictus Krankenhaus, Tutzing, Germany lKlinik für Anästhesiologie, Technische Universität München, München, Germany mDepartment of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland nMutual Insurance Company Etera, Helsinki, Finland oDepartment of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark pDepartment of Neurology, Aarhus University Hospital, Aarhus, Denmark qDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, USA rPain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital campus, London, United Kingdom sPain Phenomics and Genomics Lab, University of Toronto Centre for the Study of Pain, University of Toronto, Toronto, Canada tDepartment of Neurology, Technion Faculty of Medicine, Rambam Healt


For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in part because of differences in phenotypes used for case ascertainment. Because there is no consensus on the nature of these phenotypes, nor on the methods of collecting them, this study aimed to provide guidelines on collecting and reporting phenotypes in cases and controls for genetic studies. Consensus was achieved through a staged approach: (1) systematic literature review to identify all neuropathic pain phenotypes used in previous genetic studies; (2) Delphi survey to identify the most useful neuropathic pain phenotypes and their validity and feasibility; and (3) meeting of experts to reach consensus on the optimal phenotype(s) to be collected from patients with neuropathic pain for genetic studies. A basic "entry level" set of phenotypes was identified for any genetic study of neuropathic pain. This set identifies cases of "possible" neuropathic pain, and controls, and includes: (1) a validated symptom-based questionnaire to determine whether any pain is likely to be neuropathic; (2) body chart or checklist to identify whether the area of pain distribution is neuroanatomically logical; and (3) details of pain history (intensity, duration, any formal diagnosis). This NeuroPPIC "entry level" set of phenotypes can be expanded by more extensive and specific measures, as determined by scientific requirements and resource availability.

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