Early Stage Researcher 3 – Silvia Fanton

Individual Research Project 3
Project Title: Neuroinflammation and pain processing in fibromyalgia and osteoarthritis
Supervisor: Prof. E. Kosek (KI, Clinical)
Co-supervisor(s): Prof. C. Sommer (UKW, Clinical) and Prof S. Paulie (Mabtech)

Fibromyalgia (FM) is a widespread pain syndrome affecting circa 2% of the population. Using functional magnetic resonance imaging (fMRI), we documented functional and structural cerebral abnormalities in FM patients associated with inability to activate endogenous pain inhibitory mechanisms, thus leading to pain amplification. We also found signs of neuroinflammation in the cerebrospinal fluid of FM patients, suggesting glial activation. Increased expression of translocator protein (TSPO) is a marker for glial activation that is evaluated by positron emission tomography (PET) using TSPO ligand (PBR28). We also found that a functional polymorphism affecting the binding affinity to TSPO is associated with pain and symptom severity in FM patients.

ESR 3 will study FM patients and healthy controls to:

1. Examine how the functional polymorphism of the TSPO gene (rs6971) affects cerebral pain processing (fMRI);
2. Assess if and how this genetic polymorphism affects cerebral metabolism in pain related areas (magnetic resonance spectroscopy);
3. Use PET to study glia cell activation using two ligands:
   a) one mainly related to microglia activation (TSPO/PBR28) and b) one mainly related to astrocyte activation (deprenyl).

Delineation of TSPO-related mechanisms on cerebral pain processing and cerebral metabolism in FM patients and healthy subjects in relation to microglia and astrocyte activation.

Secondment(s): Kancera (1 month). Training in pharmacokinetics, product development strategy, product launch & management and public relations. MAB (1 month). Training on business management and patent process. UKW (4 months). Analysis of skin innervation and inflammation as additional peripheral pain generator.