TY  - JOUR
A1  - Klatt‐Schreiner, Katharina
A1  - Valek, Lucie
A1  - Kang, Jun‐Suk
A1  - Khlebtovsky, Alexander
A1  - Trautmann, Sandra
A1  - Hahnefeld, Lisa Katharina
A1  - Schreiber, Yannick
A1  - Gurke, Robert
A1  - Thomas, Dominique Jeanette
A1  - Wilken-Schmitz, Annett
A1  - Wicker, Sabine
A1  - Auburger, Georg
A1  - Geisslinger, Gerd
A1  - Lötsch, Jörn
A1  - Pfeilschifter, Waltraud
A1  - Djaldetti, Ruth
A1  - Tegeder, Irmgard
T1  - High glucosylceramides and low anandamide contribute to sensory loss and pain in Parkinson's disease
T2  - Movement disorders
N2  - Background: Parkinson's disease (PD) causes chronic pain in two‐thirds of patients, in part originating from sensory neuropathies. The aim of the present study was to describe the phenotype of PD‐associated sensory neuropathy and to evaluate its associations with lipid allostasis, the latter motivated by recent genetic studies associating mutations of glucocerebrosidase with PD onset and severity. Glucocerebrosidase catalyzes the metabolism of glucosylceramides.
Methods: We used quantitative sensory tests, pain ratings, and questionnaires and analyzed plasma levels of multiple bioactive lipid species using targeted lipidomic analyses. The study comprised 2 sets of patients and healthy controls: the first 128 Israeli PD patients and 224 young German healthy controls for exploration, the second 50/50 German PD patients and matched healthy controls for deeper analyses.
Results: The data showed a 70% prevalence of PD pain and sensory neuropathies with a predominant phenotype of thermal sensory loss plus mechanical hypersensitivity. Multivariate analyses of lipids revealed major differences between PD patients and healthy controls, mainly originating from glucosylceramides and endocannabinoids. Glucosylceramides were increased, whereas anandamide and lysophosphatidic acid 20:4 were reduced, stronger in patients with ongoing pain and with a linear relationship with pain intensity and sensory losses, particularly for glucosylceramide 18:1 and glucosylceramide 24:1.
Conclusions: Our data suggest that PD‐associated sensory neuropathies and PD pain are in part caused by accumulations of glucosylceramides, raising the intriguing possibility of reducing PD pain and sensory loss by glucocerebrosidase substituting or refolding approaches. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
KW  - endocannabinoids
KW  - lipidomic analysis
KW  - pain
KW  - quantitative sensory testing
KW  - sensory neuropathy
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56471
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-564717
SN  - 1531-8257
SN  - 0885-3185
VL  - 35
IS  - 10
SP  - 1822
EP  - 1822
PB  - Wiley
CY  - New York, NY
ER  -