title: Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.
abstract: Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.affiliation: Department of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Maier
authors.affiliation: INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France.|Université Versailles-Saint-Quentin, Versailles, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Attal
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Binder
authors.affiliation: INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France.|Université Versailles-Saint-Quentin, Versailles, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Roma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cruccu
authors.affiliation: Department of Neurology, Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Nanna B
authors.initials: NB
authors.lastname: Finnerup
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland.|Etera Mutual Pension Insurance Company, Helsinki, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Haanpää
authors.affiliation: Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.|Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hansson
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hüllemann
authors.affiliation: Department of Neurology, Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.affiliation: Department of Anaesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care, Pain Center Lake Starnberg, Benedictus Hospital Tutzing, Tutzing, Germany, and Klinik für Anästhesie, Technische Universität München, Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Freynhagen
authors.affiliation: Neuroscience Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kennedy
authors.affiliation: Department of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Magerl
authors.affiliation: Department of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany.|Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Mainka
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Reimer
authors.affiliation: Pain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom.
authors.forename: Andrew S C
authors.initials: ASC
authors.lastname: Rice
authors.affiliation: Clinical R&D Neurology, Lundbeck A/S, Copenhagen, Denmark.|Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Märta
authors.initials: M
authors.lastname: Segerdahl
authors.affiliation: Neuroscience Technologies SLP, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Serra
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark.
authors.forename: Sören
authors.initials: S
authors.lastname: Sindrup
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tölle
authors.affiliation: Department of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany.|Department of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Vollert
authors.affiliation: Department of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Rolf-Detlef
authors.initials: RD
authors.lastname: Treede
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000453:epidemiology* / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D011795:Surveys and Questionnaires