title: Evidence for brain glial activation in chronic pain patients.
abstract: Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA 2 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA marco@nmr.mgh.harvard.edu.
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Chonde
authors.affiliation: 3 Department of Anesthesia, Critical Care and Pain Medicine, MGH/HMS, Boston, MA 02114, USA.
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Akeju
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Grae
authors.initials: G
authors.lastname: Arabasz
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: 2 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA 4 Department of Psychiatry, Brigham and Women's Hospital, HMS, Boston, MA 02155, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edwards
authors.affiliation: 5 Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Hill
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Hsu
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: David
authors.initials: D
authors.lastname: Izquierdo-Garcia
authors.affiliation: 2 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA 6 Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Ru-Rong
authors.initials: RR
authors.lastname: Ji
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Misha
authors.initials: M
authors.lastname: Riley
authors.affiliation: 2 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA 4 Department of Psychiatry, Brigham and Women's Hospital, HMS, Boston, MA 02155, USA 7 Departments of Anesthesiology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15206, USA.
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Zürcher
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Albrecht
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Vangel
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA 8 Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosen
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA 2 Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, USA 9 Department of Biomedical Engineering, Kyung Hee University, Seoul 130-872, Republic of Korea.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
authors.affiliation: 1 MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D059350:Chronic Pain / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000000981:diagnostic imaging / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography; D011743:Pyrimidines; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D015850:Interleukin-6; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: 11C-PBR28; TSPO; chronic pain; glia; neuroinflammation; translocator protein (18kDa)