Linking small fiber pathology with non-coding RNA signatures in fibromyalgia syndrome as potential contributors to pain

• Applicant: Professorin Dr. Nurcan Üçeyler
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 547045079

Fibromyalgia syndrome (FMS) is a frequent and debilitating chronic pain condition often accompanied by comorbidities such as fatigue and depressed mood. The pathophysiology of pain in FMS is incompletely understood and objective diagnostic biomarkers are missing. This leads to substantial reduction of patients` health-related quality of life and high socioeconomic costs. While subgroups of women with FMS show small fiber pathology which may manifest as peripheral denervation, men are underdiagnosed and disease pathophysiology is hardly investigated in male FMS patients. Intriguingly, the degree of skin denervation correlates with disease severity. Furthermore, we showed dysregulation of systemic small RNA profiles where microRNAs (miRs) discriminated FMS patients from healthy women and disease controls. In our current project, we aim to build on these findings and determine whether small fiber pathology and systemic signatures of miRs and transfer RNA fragments (tRFs) are also present in men with FMS. Since knowledge on both small fiber denervation and small and long non-coding RNA profiles over time is scarce, we intend to fill this gap via longitudinal biomaterial analysis. Furthermore, our clinical-experimental approach combines clinical findings with next generation molecular biological and microscopy techniques to decipher the pathophysiology of pain in FMS in men and women. Specifically, we will further investigate cellular interactions between small fibers and surrounding epidermal skin cells to achieve better understanding of denervation. Further, systemic changes in post transcriptionally acting small RNAs in whole blood will be traced back to single blood cell subtypes and finally, molecular binding partners (RNAs, RNA binding proteins) within these cells will be determined. This will allow insights in immune-associated alterations in FMS with unprecedented precision. Thus, our study aims to both advance FMS diagnostics and identify novel druggable targets at local and systemic levels. The insights gained in our project bear great potential for the clinical management and future basic science research of FMS.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professorin Hermona Soreq, Ph.D.