Autoimmune and molecular mechanisms for pain and fatigue in fibromyalgia

Concept

Although there is a wide range of symptoms, the main somatic symptoms of Fibromyalgia (FM) are chronic musculoskeletal pain and physical and cognitive fatigue. There is an urgent need to advance our understanding of the underlying cellular and molecular mechanisms of FM pain and fatigue in order to identify new therapy solutions. The group will conduct metabolomic and lipidomic studies in serum samples from women with FM to identify factors that correlate with pain, fatigue and/or antibodies (IgG). The project will use animal models and in vitro systems to further explore if candidate factors that are elevated in FM samples contribute to pain and fatigue and examine the benefit of exercise and pharmacological interventions. The direct reverse translation of clinical findings will allow to generate conclusions of high predictive value/validity.

Facts and Figures

Project Lead
C Svensson
Karolinska Institutet
camilla. svensson@ki.se
FOREUM research grant: € 599.950
2021–2024

Meet the Team

C Svensson
Karolinska Institutet
J Lanner
Karolinska Institutet
E Kosek
Uppsala University
K Kultima
Uppsala University
D Andersson
King's College London
P Tavi
University of Eastern Finland (UEF)

Objectives

Question: Are changes in lipid metabolism and mitochondrial function in sensory neurons and muscle contributing to pain and/or fatigue – and are there links to autoimmunity?
Objective 1. Examine metabolic and lipidomic profile in FM in relation to IgG and clinical symptoms.
Objective 2. Determine whether transfer of IgG from FMS alters metabolism and mitochondrial function in mice and whether such changes are related to induction of pain and physical fatigue.
Objective 3. Determine whether candidate lipids or other serum factors influence nociceptor excitability, and to examine the impact of pharmacological interventions and exercise on FM IgG-induced nociceptor excitability, muscle pathophysiology and behaviour.

Patient Voice

FM antibodies and fatty acids of relevance for disease mechanism in FM will be identified and validated. The FM antibodies could be used for development of diagnostic tests for subgrouping FM patients, a prerequisite for patient tailored treatment strategies. The increased understanding of disease relevant substances and how various interventions can reverse their negative effects can potentially lead to the development of new treatment strategies for FM.

Goals/Milestones

1. Metabolomic/lipidomic analysis of 120 FM/HC (cohort A).
2. Validation of the identified pain/fatigue relevant factors in 200 FM/HC samples (cohort B) and establishment of their relation to IgG antibodies, pain sensitivity and skin innervation.
3. Metabolomic/lipidomic analysis blood, muscle, DRG and brain from FM/HC IgG injected mice.
4. Comparison of changes in lipids/metabolites between human and mouse samples.
5. Results from in vivo and in vitro muscle fatigue studies.
6. Results from intervention studies (exercise and pharmacology).
7. Analysis of Ca2+-measurements in DRG neurons.
8. Electrophysiological studies of single units in skin-nerve preparation.
9. Webinar for patient organizations in Sweden, Finland, UK summarizing research and findings
10. Submit popular scientific summary/highlight to patient organizations’ newsletters