Peripheral Neuropathic Pain: A mechanism-related organizing principle based on sensory profiles

TY - JOUR

T1 - Peripheral Neuropathic Pain: A mechanism-related organizing principle based on sensory profiles

AU - Baron, Ralf

AU - Maier, Christoph

AU - Attal, Nadine

AU - Binder, Andreas

AU - Bouhassira, Didier

AU - Cruccu, Giorgio

AU - Finnerup, Nanna B

AU - Haanpää, Maija

AU - Hansson, Per

AU - Hüllemann, Philipp

AU - Jensen, Troels S

AU - Freynhagen, Rainer

AU - Kennedy, Jeffrey D

AU - Magerl, Walter

AU - Mainka, Tina

AU - Reimer, Maren

AU - Rice, Andrew S C

AU - Segerdahl, Märta

AU - Serra, Jordi

AU - Sindrup, Sören

AU - Sommer, Claudia

AU - Tölle, Thomas

AU - Vollert, Jan

AU - Treede, Rolf-Detlef

AU - German Neuropathic Pain Research Network (DFNS), and the EUROPAIN and NEUROPAINconsortia.

PY - 2017/2

Y1 - 2017/2

N2 - 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 neuropathic pain patients using hypothesis-free statistical methods on the database of three large multi-national research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, Neuropain).Standardized quantitative sensory testing (QST) 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 QST 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 three profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

AB - 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 neuropathic pain patients using hypothesis-free statistical methods on the database of three large multi-national research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, Neuropain).Standardized quantitative sensory testing (QST) 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 QST 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 three profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

U2 - 10.1097/j.pain.0000000000000753

DO - 10.1097/j.pain.0000000000000753

M3 - SCORING: Journal article

C2 - 27893485

VL - 158

SP - 261

EP - 272

JO - PAIN

JF - PAIN

SN - 0304-3959

IS - 2

ER -