{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:07:06Z","timestamp":1790014026689,"version":"4.0.1"},"reference-count":169,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nociplastic pain has recently been introduced as a third entity for identifying patients suffering from chronic pain that arises from altered nociception, without evidence of peripheral nociceptors activation or alterations of the somatosensory system. Currently, the main challenge of nociplastic pain is that it remains a diagnosis of exclusion, since no specific biomarkers are available. Positron emission tomography (PET) neuroimaging studies, using selective translocator protein (TSPO) radiopharmaceuticals, specific for microglia activation, showed a strong correlation between neuroinflammation and nociplastic pain: in particular, in fibromyalgia (FM), which is the prototype disease. Neuroimaging studies identified key brain changes associated with pain processing and neuroinflammation in patients suffering from widespread pain, often associated with sleep, mood disorders, and cognitive impairment. The present review will provide an overview on the role of neuroinflammation in nociplastic pain, focusing on preclinical evidence of microglia activation and advances in PET neuroimaging. Understanding the role of neuroinflammation could have relevant implications in selecting targeted therapeutic strategies and improving analgesic efficacy.<\/jats:p>","DOI":"10.3390\/ijms262411861","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T09:54:55Z","timestamp":1765274095000},"page":"11861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microglial Activation in Nociplastic Pain: From Preclinical Models to PET Neuroimaging and Implications for Targeted Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7184-5519","authenticated-orcid":false,"given":"Flaminia","family":"Coluzzi","sequence":"first","affiliation":[{"name":"Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"Unit Anesthesia, Intensive Care and Pain Therapy, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3403-7555","authenticated-orcid":false,"given":"Lynda","family":"Zeboudj","sequence":"additional","affiliation":[{"name":"Wolfson Sensory, Pain and Regeneration Centre, King\u2019s College London, Guy\u2019s Campus, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9488-1720","authenticated-orcid":false,"given":"Maria Sole","family":"Scerpa","sequence":"additional","affiliation":[{"name":"Unit Anesthesia, Intensive Care and Pain Therapy, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-6967","authenticated-orcid":false,"given":"Anna","family":"Giorgio","sequence":"additional","affiliation":[{"name":"Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5294-2962","authenticated-orcid":false,"given":"Roberto Alberto","family":"De Blasi","sequence":"additional","affiliation":[{"name":"Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"Unit Anesthesia, Intensive Care and Pain Therapy, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-5727","authenticated-orcid":false,"given":"Marzia","family":"Malcangio","sequence":"additional","affiliation":[{"name":"Wolfson Sensory, Pain and Regeneration Centre, King\u2019s College London, Guy\u2019s Campus, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-3607","authenticated-orcid":false,"given":"Monica","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"Unit Anesthesia, Intensive Care and Pain Therapy, Sant\u2019Andrea University Hospital, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1097\/j.pain.0000000000000507","article-title":"Do We Need a Third Mechanistic Descriptor for Chronic Pain States?","volume":"157","author":"Kosek","year":"2016","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"De Blasiis, P., de Sena, G., Signoriello, E., Sirico, F., Imamura, M., and Lus, G. 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