Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive symptoms. Central sensitization is considered a key mechanism in the pathophysiology of fibromyalgia; however, the underlying biological markers have not been fully clarified.

Brain-derived neurotrophic factor (BDNF) and S100B protein have been suggested to play roles in neuroinflammation and central pain processing. This observational, cross-sectional study aims to evaluate serum S100B and BDNF levels in patients with fibromyalgia and to investigate their relationship with central sensitization and sleep quality. Serum biomarker levels and clinical assessment scales will be compared between patients with fibromyalgia and healthy controls.

Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive complaints. Central sensitization, defined as increased responsiveness of the central nervous system to sensory stimuli, is considered a core mechanism in the pathophysiology of fibromyalgia. However, the biological processes underlying central sensitization and associated clinical features such as sleep disturbances remain incompletely understood.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in synaptic plasticity, neuronal survival, and pain modulation, and has been suggested to be associated with central sensitization. S100B is a calcium-binding protein predominantly released by astrocytes and is considered a peripheral marker of neuroinflammation and glial activation. Alterations in serum levels of BDNF and S100B have been reported in chronic pain conditions, including fibromyalgia.

This observational, cross-sectional study aims to evaluate serum S100B and BDNF levels in patients diagnosed with fibromyalgia according to the 2016 American College of Rheumatology criteria and to investigate their relationship with central sensitization and sleep quality. A healthy control group matched for age and sex will be included for comparative analysis.

All participants will undergo a single-time-point assessment, including collection of demographic and clinical data. Blood samples will be obtained to measure serum S100B and BDNF levels using standard laboratory methods. Central sensitization will be assessed using the Central Sensitization Inventory, while sleep quality will be evaluated using the Pittsburgh Sleep Quality Index. Additional clinical assessments will include the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, and Beck Anxiety Inventory.

The study does not involve any therapeutic intervention or randomization. The findings are expected to contribute to a better understanding of the biological correlates of central sensitization and sleep disturbances in fibromyalgia.

Inclusion Criteria:

• Female participants aged between 18 and 50 years

Diagnosis of fibromyalgia according to 2016 American College of Rheumatology (ACR) criteria

Symptoms present for at least 3 months

Ability to understand and complete study questionnaires

Provision of written informed consent

For healthy controls:

No diagnosis of fibromyalgia or chronic widespread pain

No known systemic disease

Exclusion Criteria:

-

Participant eligibility is NOT based on self-representation of gender identity.

Presence of any systemic disease (hematologic, endocrine, rheumatologic, renal, cardiovascular, gastrointestinal, or respiratory) Active infection History of malignancy Major surgery or trauma within the last 1 year Any treatment for fibromyalgia within the last 3 months Pregnancy or breastfeeding Smoking Vitamin D deficiency

Individual participant data (IPD) will not be shared publicly. De-identified aggregate data may be made available upon reasonable request from the corresponding author after publication of the study results.