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Pain. 2017 Feb;158(2):261-272. doi: 10.1097/j.pain.0000000000000753.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

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aDivision of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany bDepartment of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany cINSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France dUniversité Versailles-Saint-Quentin, Versailles, France eDepartment of Neurology and Psychiatry, Sapienza University, Roma, Italy fDepartment of Neurology, Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark, gHelsinki University Central Hospital, Helsinki, Finland hEtera Mutual Pension Insurance Company, Helsinki, Finland iDepartment of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway jDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden kDepartment 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 lNeuroscience Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA. mDepartment of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany nDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany oPain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom pClinical R&D Neurology, Lundbeck A/S, Copenhagen, Denmark qDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden rNeuroscience Technologies SLP, Barcelona, Spain sDepartment of Neurology, Odense University Hospital, Odense, Denmark tDepartment of Neurology, University Hospital Würzburg, Würzburg, Germany uDepartment of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.


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.

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