{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:04:08Z","timestamp":1784880248589,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>(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\u03b2 (IL-1\u03b2), 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 &lt; 0.05). No significant differences were observed in IL-1\u03b2 levels. Receiver operating characteristic analysis demonstrated exploratory discriminatory performance within this case\u2013control 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.<\/jats:p>","DOI":"10.3390\/ijms27156579","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"6579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered Circulating Biomarkers of Purinergic Signaling, Inflammasome-Related Pathways, Pyroptosis, and Oxidative Stress in Fibromyalgia"],"prefix":"10.3390","volume":"27","author":[{"given":"Emrullah","family":"Hayta","sequence":"first","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation, Ata\u015fehir Acibadem Hospital, Acibadem University, Istanbul 34758, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugba","family":"Agbektas","sequence":"additional","affiliation":[{"name":"Department of Food Processing Technologies Services, Y\u0131ld\u0131zeli Vocational School, Sivas Cumhuriyet University, Sivas 58140, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonca","family":"Kabak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas 58140, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokhan","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas 58140, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-1325","authenticated-orcid":false,"given":"Ayca","family":"Tas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas 58140, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavuz","family":"Silig","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas 58140, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1001\/jama.2014.3266","article-title":"Fibromyalgia: A clinical review","volume":"311","author":"Clauw","year":"2014","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15022","DOI":"10.1038\/nrdp.2015.22","article-title":"Fibromyalgia","volume":"1","author":"Ablin","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neuroscience.2016.06.006","article-title":"Neurobiology of fibromyalgia and chronic widespread pain","volume":"338","author":"Sluka","year":"2016","journal-title":"Neuroscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00281-018-0672-2","article-title":"Neurogenic inflammation in fibromyalgia","volume":"40","author":"Littlejohn","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: Mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"\u00dc\u00e7eyler, N., H\u00e4user, W., and Sommer, C. (2011). Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome. BMC Musculoskelet. Disord., 12.","DOI":"10.1186\/1471-2474-12-245"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.immuni.2017.06.020","article-title":"The P2X7 receptor in infection and inflammation","volume":"47","author":"Sarti","year":"2017","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1002\/1873-3468.13115","article-title":"The pannexin1 membrane channel: Distinct conformations and functions","volume":"592","author":"Dahl","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-mediated programmed necrotic cell death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature22393","article-title":"Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin","volume":"547","author":"Wang","year":"2017","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2147\/JPR.S128508","article-title":"Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma","volume":"10","author":"Tanum","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_13","first-page":"1023","article-title":"Can coenzyme Q10 improve clinical and molecular parameters in fibromyalgia?","volume":"18","author":"Cordero","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1089\/ars.2013.5198","article-title":"NLRP3 inflammasome is activated in fibromyalgia: The effect of coenzyme Q10","volume":"20","author":"Cordero","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, R., Fusco, R., Siracusa, R., Cordaro, M., Genovese, T., Peritore, A.F., Gugliandolo, E., Interdonato, L., Sforza, A.M., and Crupi, R. (2021). Inhibition of P2X7 purinergic receptor ameliorates fibromyalgia syndrome by suppressing NLRP3 pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126471"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bcp.2017.12.021","article-title":"The P2X7 receptor: A main player in inflammation","volume":"151","author":"Adinolfi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Starobova, H., and Vetter, I. (2020). The NLRP3 inflammasome: Role and therapeutic potential in pain treatment. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.01016"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1097\/j.pain.0000000000002927","article-title":"Evidence of neuroinflammation in fibromyalgia syndrome: A [18F] DPA-714 PET study","volume":"164","author":"Mueller","year":"2023","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-immunol-073119-095439","article-title":"Caspases in cell death, inflammation, and pyroptosis","volume":"38","author":"Kesavardhana","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mito.2015.01.010","article-title":"Oxidative stress, mitochondrial dysfunction and inflammation: Common events in skin of patients with fibromyalgia","volume":"21","author":"Cordero","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhuang, D., Misra, S.L., Mugisho, O.O., Rupenthal, I.D., and Craig, J.P. (2023). NLRP3 inflammasome as a potential therapeutic target in dry eye disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310866"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1080\/21501203.2020.1816584","article-title":"Antioxidant, antimicrobial and neuroprotective effects of Octaviania asterosperma in vitro","volume":"12","author":"Sevindik","year":"2021","journal-title":"Mycology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Niu, L., Zhang, S., Wu, J., Chen, L., and Wang, Y. (2015). Upregulation of NLRP3 inflammasome in the tears and ocular surface of dry eye patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126277"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6579\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:38:29Z","timestamp":1784878709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":25,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156579"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156579","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}