Peripheral pain mechanisms in fibromyalgia
- Reference number
- UKR22-0075
- Project leader
- Agashkov, Kirill
- Start and end dates
- 220801-241231
- Amount granted
- 1 000 000 SEK
- Administrative organization
- Karolinska Institutet
- Research area
- Life Sciences
Summary
Fibromyalgia (FM) is a chronic disorder affecting 2-4% of the population. The main symptoms are widespread musculoskeletal pain, tenderness, and fatigue. FM can cause a negative impact on most elements of the individual’s life leading to difficulties performing daily and work-related activities. While the causes remain unknown, the most well-defined pathological mechanisms in FM are alterations of central pain pathways. Emerging data, however, suggest that peripheral mechanisms are also at play causing enhanced neuronal excitability and a contribution of autoantibodies (IgG) has been suggested. In this project, the links between FM IgG, mitochondrial dysfunction, and enhanced neuronal excitability will be explored. For this, IgG isolated from FM patients or healthy controls will be transferred to mice, and methodology allowing electrophysiological recordings and assessment of mitochondrial function in dorsal root ganglia as well as pharmacological interventions used to address the specific aims: 1. Examine ionic mechanisms contributing to neural hyperexcitability after FM IgG transfer 2. Examine if and how FM IgG changes mitochondrial function in DRG cells 3. Explore if oxidative stress induced by FM IgG is linked to enhanced neuronal excitability FM is a severe, incurable disease. This line of research will provide new insights into mechanisms underpinning FM symptoms and has the potential to pave a pathway to future mechanism-based therapeutics to treat FM.
Popular science description
Fibromyalgia (FM) is a chronic disorder affecting 2-4% of the population. The main symptoms are widespread musculoskeletal pain, tenderness, and fatigue. FM can cause a negative impact on most elements of the individual’s life leading to difficulties performing daily and work-related activities. While the causes remain unknown, the most well-defined changes in FM are alterations in the processing of pain signals in the brain. Emerging data, however, suggest that antibodies circulating in the blood also contribute to the pain problem by enhancing pain sensitivity. In this project, the links between antibodies and dysfunction in mitochondria "often referred to as the powerhouses of the cell and chronic pain will be explored. For this, antibodies from FM patients or healthy controls will be transferred to mice, and methodologies allowing assessment of the activity in pain fibers and mitochondrial function in nerve cells will be used. In addition, drugs that reduce the impact of mitochondrial dysfunction will be tested in order to identify new targets for pain relief. FM is a severe, incurable disease. This line of research will provide new insights into mechanisms underpinning FM symptoms and has the potential to pave a pathway to future mechanism-based therapeutics to treat FM.