{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:23:57Z","timestamp":1792045437195,"version":"4.4.0"},"reference-count":86,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21NS087472-01A1 (M.L.L.)"],"award-info":[{"award-number":["1R21NS087472-01A1 (M.L.L.)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01NS095937-01A1 (M.L.L.)"],"award-info":[{"award-number":["1R01NS095937-01A1 (M.L.L.)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01NS094306-01A1 (M.L.L.)"],"award-info":[{"award-number":["1R01NS094306-01A1 (M.L.L.)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14\u20131-0543 (M.L.L.)"],"award-info":[{"award-number":["W81XWH-14\u20131-0543 (M.L.L.)"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and\/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct \u2018neuroinflammatory signatures\u2019. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. \u2018radicular\u2019 versus \u2018axial\u2019 back pain).<\/jats:p>\n                  <jats:p>Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 \u00b1 16.6 years old (mean \u00b1 SD)] and 28 with radicular back pain (48.3 \u00b1 13.2 years old), underwent PET\/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of \u2018fibromyalgianess\u2019 (i.e. the degree of pain centralization, or \u2018nociplastic pain\u2019). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables.<\/jats:p>\n                  <jats:p>For the primary somatosensory cortex representation of back\/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex\u2013thalamus connectivity across groups.<\/jats:p>\n                  <jats:p>Our findings support the existence of \u2018neuroinflammatory signatures\u2019 that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.<\/jats:p>","DOI":"10.1093\/brain\/awab336","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T08:23:05Z","timestamp":1631175785000},"page":"1098-1110","source":"Crossref","is-referenced-by-count":86,"title":["Neuroimmune signatures in chronic low back pain subtypes"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-9037","authenticated-orcid":false,"given":"Zeynab","family":"Alshelh","sequence":"first","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Brusaferri","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atreyi","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M","family":"Hooker","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1540-2809","authenticated-orcid":false,"given":"Angel","family":"Torrado-Carvajal","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"},{"name":"Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos , Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Placzek","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwaseun","family":"Akeju","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeungchan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Sclocco","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"},{"name":"Department of Radiology, Logan University , Chesterfield, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"Catana","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School , Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Napadow","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. 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