Altered Circulating Biomarkers of Purinergic Signaling, Inflammasome-Related Pathways, Pyroptosis, and Oxidative Stress in Fibromyalgia

Abstract

(1) Fibromyalgia syndrome (FMS) is a chronic pain disorder with a multifactorial pathogenesis involving neuroinflammation, oxidative stress, and immune dysfunction. This study aimed to evaluate serum biomarkers related to purinergic signaling, inflammasome activation, pyroptosis, and oxidative stress in patients with FMS. (2) Methods: A total of 93 patients with FMS and 93 age- and sex-matched healthy controls were enrolled. Serum levels of pannexin-1 (PANX1), purinergic receptor P2X7 (P2RX7), NLRP3, caspase-1 (CASP1), interleukin-1 beta (IL-1 beta), interleukin-18 (IL-18), gasdermin D (GSDMD), and gasdermin E (GSDME) were measured using enzyme-linked immunosorbent assays (ELISA). (3) Results: Total antioxidant status (TAS) and total oxidant status (TOS) were determined. Patients with FMS exhibited significantly increased serum CASP1, GSDME, PANX1, P2RX7, and total oxidative stress (TOS) levels, whereas GSDMD, NLRP3, IL-18, and TAS levels were significantly decreased compared with controls (all p < 0.05). No significant differences were observed in IL-1 beta levels. Receiver operating characteristic analysis demonstrated exploratory discriminatory performance within this case-control cohort for CASP1 and TAS (AUC = 0.898), followed by TOS (AUC = 0.849) and P2RX7 (AUC = 0.757). (4) Conclusions: These findings indicate alterations in circulating biomarkers related to purinergic signaling, inflammasome-associated pathways, pyroptosis-related proteins, and oxidative stress in patients with FMS. These alterations may contribute to the pathophysiology of FMS and provide a foundation for future mechanistic studies investigating their potential as biomarkers and therapeutic targets.