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Metabolomic Differences in Fibromyalgia Compared to Osteoarthritis, Carpal Tunnel Syndrome, and Matched Controls
Abstract   Peer reviewed

Metabolomic Differences in Fibromyalgia Compared to Osteoarthritis, Carpal Tunnel Syndrome, and Matched Controls

Giovanni Berardi, Bridget Zimmerman, Andrew Schrepf, Eric Taylor, Laura Frey Law and Kathleen Sluka
The journal of pain, Vol.41(Supplement), 105807
03/2026
DOI: 10.1016/j.jpain.2025.105807

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Abstract

Fibromyalgia (FM) is characterized by widespread pain, fatigue, unrefreshing sleep, physical and cognitive dysfunction. While multiple systems are purported in FM pathophysiology including central and peripheral nervous system, immune system, and energy metabolism, no etiologic target has been identified. Understanding of biological perturbations that explain the symptom presentation is needed to guide personalized treatment strategies. This study investigated serum metabolite levels among individuals with FM (n=70), osteoarthritis (OA, n=70), carpal tunnel syndrome (CTS, n=70), and matched controls (CON, n=74). Pain intensity and interference were measured with the Brief Pain Inventory. Symptom severity and impact on function were measured with the Symptom Impact Questionnaire. Serum was isolated from whole blood and serum metabolites were analyzed using gas and liquid chromatography/mass spectrometry. Individuals were matched for age and BMI however, the OA group was older than FM (FM: 46y, OA:57y, p<.001). Individuals with FM reported greater pain intensity, pain interference, and symptom impact compared to OA, CTS, and CON (all comparisons p<.001). A diverse set of metabolites (n=33) from multiple classes including amino acids, carbohydrates, lipids, and nucleic acids were statistically different (p<.05, Cohen’s d>0.4) in the FM group. Metabolic pathways with altered substrate concentrations in FM include valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; and the citric acid cycle. Differential levels of valine, leucine, methylmalonate, glucose, hypothaurine, serotonin, and fumarate were common among group comparisons (p<.05). These preliminary findings support future studies investigating metabolomic mechanisms and symptom management in fibromyalgia. Funding: National Institutes of Health (R01AR077418).

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