title: Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations.
abstract: 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.
authors.affiliation: Division of Population Health Sciences, University of Dundee, Dundee, Scotland, United Kingdom Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt, France Université Versailles Saint-Quentin, Versailles, France Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany deCODE Genetics/Amgen, Reykjavík, Iceland Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom Academic Unit of Palliative Care, Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom The Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada Department of Neurology, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, USA Zentrum für Anästhesiologie, Intensivmedizin, Schmerztherapie und Palliativmedizin, Benedictus Krankenhaus, Tutzing, Germany Klinik für Anästhesiologie, Technische Universität München, München, Germany Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland Mutual Insurance Company Etera, Helsinki, Finland Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark Department of Neurology, Aarhus University Hospital, Aarhus, Denmark Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, USA Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital campus, London, United Kingdom Pain Phenomics and Genomics Lab, University of Toronto Centre for the Study of Pain, University of Toronto, Toronto, Canada Department of Neurology, Technion Faculty of Medicine, Rambam Health Care Campus, Haifa, Israel (O. van Hecke is now with Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom).
authors.forename: Oliver
authors.initials: O
authors.lastname: van Hecke
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
authors.forename: Nadine
authors.initials: N
authors.lastname: Attal
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.forename: Gyda
authors.initials: G
authors.lastname: Bjornsdottir
authors.forename: David L H
authors.initials: DLH
authors.lastname: Bennett
authors.forename: Michael I
authors.initials: MI
authors.lastname: Bennett
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.forename: Rainer
authors.initials: R
authors.lastname: Freynhagen
authors.forename: Maija
authors.initials: M
authors.lastname: Haanpää
authors.forename: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
authors.forename: Andrew S C
authors.initials: ASC
authors.lastname: Rice
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Seltzer
authors.forename: Thorgeir E
authors.initials: TE
authors.lastname: Thorgeirsson
authors.forename: David
authors.initials: D
authors.lastname: Yarnitsky
authors.forename: Blair H
authors.initials: BH
authors.lastname: Smith
mesh_terms: D032921:Consensus; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D003697:Delphi Technique; D006801:Humans; D007391:International Cooperation; D009437:Neuralgia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010147:Pain Measurement; D010641:Phenotype