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Noteworthy, Purinergic receptors, specifically P2X, are implicated in pain signaling and neuroinflammation via inflammasome signaling. However, there is no available data on the impact of pharmacological intervention on the P2X receptor in thalamic pain transmission in FM. To investigate this aspect, the clinically tested P2X inhibitor, Suramin (SURM), was utilized. FM was induced over three days using Reserpine (1\u00a0mg\/kg\/day, s.c.), followed by a single dose of SURM (100\u00a0mg\/kg, i.p.). At the molecular level, SURM countered the overexpression of P2X7 and P2X4 receptors accompanied by reduced NLRP3 inflammasome complex and pyroptotic markers like gasdermin-D. This was associated with the suppression of the p38-MAPK and NF-\u03baB pathways, along with a decrease in pro-inflammatory cytokines and tumor necrosis factor-\u03b1 as observed by increased CD86 expression on M1 microglia phenotype, a neuroinflammatory marker. Concurrently, blocking the P2X receptor shifted microglia polarization towards the M2 phenotype, marked by elevated CD163 expression, as a neuroprotective mechanism. This was outlined by increased neurotrophic and anti-inflammatory IL-10 with normalization of disturbed neurotransmitters. Behaviorally, SURM ameliorated the heightened pain processing, as observed in mechanical and thermal pain tests. Furthermore, it lowered Reserpine-induced motor impairment in the rotarod and open-field tests. This improvement in the somatosensory experience was reflected in alleviating depressive-like behavior in the forced swimming test. These findings highlight the therapeutic potential of blocking thalamic P2X receptors in alleviating fibromyalgia symptoms.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>\n          <jats:p>Thalamic Purinergic Inhibition abrogates Fibromyalgia-associated pain<\/jats:p>\n          <jats:p>Blocking Thalamic P2X receptors by Suramin has therapeutic potential of alleviating pain and neuroinflammation associated with fibromyalgia symptoms<jats:bold>.<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s11481-025-10207-4","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T01:22:49Z","timestamp":1746580969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Possible Interaction of Suramin with Thalamic P2X Receptors and NLRP3 Inflammasome Activation Alleviates Reserpine-Induced Fibromyalgia-Like Symptoms"],"prefix":"10.1007","volume":"20","author":[{"given":"Maram M.","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala F.","family":"Zaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S.","family":"Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"issue":"7","key":"10207_CR1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1097\/00007611-200407000-00008","volume":"97","author":"O Adig\u00fczel","year":"2004","unstructured":"Adig\u00fczel O et al (2004) The possible effect of clinical recovery on regional cerebral blood flow deficits in fibromyalgia: a prospective study with semiquantitative SPECT. 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