High glucosylceramides and low anandamide contribute to sensory loss and pain in Parkinson's disease

  • 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.

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Author:Katharina Klatt‐Schreiner, Lucie Valek, Jun‐Suk Kang, Alexander Khlebtovsky, Sandra Trautmann, Lisa Hahnefeld, Yannick Schreiber, Robert GurkeORCiDGND, Dominique Jeanette ThomasORCiDGND, Annett Wilken‐Schmitz, Sabine WickerORCiDGND, Georg AuburgerORCiDGND, Gerd GeisslingerORCiDGND, Jörn LötschORCiDGND, Waltraud PfeilschifterORCiDGND, Ruth Djaldetti, Irmgard TegederORCiD
Parent Title (English):Movement disorders
Place of publication:New York, NY
Document Type:Article
Date of Publication (online):2020/07/11
Date of first Publication:2020/07/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/11/11
Tag:endocannabinoids; lipidomic analysis; pain; quantitative sensory testing; sensory neuropathy
Page Number:12
First Page:1822
Last Page:1822
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0