The Role of AlphαSynuclein in Mouse Models of Acute, Inflammatory and Neuropathic Pain

  • (1) AlphαSynuclein (αSyn) is a synaptic protein which is expressed in the nervous system and has been linked to neurodegenerative diseases, in particular Parkinson’s disease (PD). Symptoms of PD are mainly due to overexpression and aggregation of αSyn and include pain. However, the interconnection of αSyn and pain has not been clarified so far. (2) We investigated the potential effects of a αSyn knock-out on the nociceptive behaviour in mouse models of acute, inflammatory and neuropathic pain. Furthermore, we assessed the impact of αSyn deletion on pain-related cellular and molecular mechanisms in the spinal cord in these models. (3) Our results showed a reduction of acute cold nociception in αSyn knock-out mice while responses to acute heat and mechanical noxious stimulation were similar in wild type and knock-out mice. Inflammatory nociception was not affected by αSyn knock-out which is also mirrored by unaltered inflammatory gene expression. In contrast, in the SNI model of neuropathic pain, αSyn knock-out mice showed decreased mechanical allodynia as compared to wild type mice. This effect was associated with reduced proinflammatory mechanisms and suppressed activation of MAP kinase signalling in the spinal cord while endogenous antinociceptive mechanisms are not inhibited. (4) Our data indicate that αSyn plays a role in neuropathy and its inhibition might be useful to ameliorate pain symptoms after nerve injury.

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Author:Moritz MöllerGND, Christine MöserGND, Ulrike Weiß, Ellen NiederbergerGND
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2022/06/19
Date of first Publication:2022/06/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/01/17
Tag:MAP kinase; alphaSynuclein; inflammation; neuropathic pain; nociception
Issue:12, art. 1967
Article Number:1967
Page Number:17
First Page:1
Last Page:17
The following are available online at, Figure S1: Expression, regulation and functions of aSyn in the DRGs; Figure S2: Zymosan induced paw inflammation; Figure S3: Mechanical and cold allodynia in the SNI model; Figure S4: Expression of delta-opioid receptor (DOR) and cannabinoid receptor 1 (CB1 R) genes in the spinal cord of mice in the SNI model; Figure S5: Immunofluorescence background control staining.
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International