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

Ralf Baron, Christoph Maier, Nadine Attal, Andreas Binder, DIdier Bouhassira, Giorgio Cruccu, Nanna B. Finnerup, Maija Haanpaä, Per Hansson, Philipp Hüllemann, Troels S. Jensen, Rainer Freynhagen, Jeffrey D. Kennedy, Walter Magerl, Tina Mainka, Maren Reimer, Andrew S.C. Rice, Märta Segerdahl, Jordi Serra, Sören SindrupClaudia Sommer, Thomas Tölle, Jan Vollert, Rolf Detlef Treede

Research output: Contribution to journalArticlepeer-review

421 Scopus citations

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.

Original languageEnglish
Pages (from-to)261-272
Number of pages12
JournalPain
Volume158
Issue number2
DOIs
StatePublished - 1 Feb 2017

Keywords

  • Clinical trials
  • Epidemiology
  • Neuropathic pain
  • QST
  • Sensory signs

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