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NEW MODEL OF FIBROMYALGIA – IDENTIFICATION OF CHANGES IN PROTEIN EXPRESSION INDUCED BY PATIENT ANTIBODIES IN DORSAL ROOT GANGLIA
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska institutet.
2023 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Abstract Background: Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain and fatigue. Today´s drugs used to treat FM patients are often inadequate in treating symptoms. A recent discovery suggest that part of the pathophysiology of FM depends on immunoglobulin G (IgG) autoantibodies, this notion is based on the novel finding that injection of IgG from FM patients into mice induces widespread hypersensitivity as well as a reduction in locomotor activity, grip strength and innervation of the epidermis when compared to mice injected with IgG from healthy controls (HC). Moreover, IgG has been shown to bind and activate satellite glia cells (SGC) in dorsal root ganglia (DRG). Proteins such as autotaxin (ATX) and the voltage dependent calcium channel subunit (α2δ1) have been identified to be part of the pain mechanism in chronic pain conditions, e.g, in Rheumatoid arthritis (RA). Interestingly, FM is a common comorbidity in RA. Autotaxin is a lysophosphatic acid (LPA) converting enzyme and Enpp2 is the gene encoding for ATX. Cacna2d1is the gene encoding for α2δ1 which is a subunit in a voltage-gated calcium channel, involved in regulating the release of neurotransmitters. By targeting these proteins novel therapeutics could be developed in order to treat FM. The aim of this study is to investigate the expression of these proteins in the DRGs of FM and HC IgG injected mice, at the gene and protein levels. To further understand their involvement in pain-like behavior and eventually treat FM patients. 

Methods: This was done by using qPCR and immunohistochemistry of the DRG of FM- and HC IgG injected mice, and immunocytochemistry of mixed primary DRG cell cultures stimulated with FM or HC IgG. 

Results: On a gene level, the expression of Enpp2 and Cacna2d1 were elevated in DRG of the mice injected with FM IgG compared to HC IgG On a protein level, there was no significant difference in the expression of ATX and α2δ1 in vivo or in vitro between groups. 

Conclusion: Our study showed that ATX and α2δ1 protein levels are unchanged upon FM IgG injection into mice and mixed DRG culture stimulation. However, the number of animals per group was small in these pilot studies and should be increased before final conclusions are drawn. Further research is needed to advance our understanding of the pain mechanism in FM so that novel targets for drug development can be identified and pain relief can be provided to these patients. 

Place, publisher, year, edition, pages
2023. , p. 53
Keywords [en]
Fibromyalgia, New model of fibromyalgia
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-506307OAI: oai:DiVA.org:uu-506307DiVA, id: diva2:1775226
Subject / course
Pharmaceutical Pharmacology
Educational program
Master of Science Programme in Pharmacy
Presentation
2023-05-31, Biomedicinskt centrum BMC, Husargatan 3, Uppsala, 09:15 (English)
Supervisors
Examiners
Available from: 2023-06-27 Created: 2023-06-26 Last updated: 2023-06-27Bibliographically approved

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