Evidence for brain glial activation in chronic pain patients

Marco L. Loggia, Daniel B. Chonde, Oluwaseun Akeju, Grae Arabasz, Ciprian Catana, Robert R. Edwards, Elena Hill, Shirley Hsu, David Izquierdo-Garcia, Ru Rong Ji, Misha Riley, Ajay D. Wasan, Nicole R. Zurcher, Daniel S. Albrecht, Mark G. Vangel, Bruce R. Rosen, Vitaly Napadow, Jacob M. Hooker

Research output: Contribution to journalArticle

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 11C-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 11C-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.

Original languageEnglish (US)
Pages (from-to)604-615
Number of pages12
JournalBrain
Volume138
Issue number3
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Neuroglia
Chronic Pain
Pain
Brain
Proteins
Maintenance
Somatoform Disorders
Microglia
Low Back Pain
Thalamus
Astrocytes
Positron-Emission Tomography
Interleukin-6
Leg
Spine
Anti-Inflammatory Agents
Animal Models
Magnetic Resonance Imaging
Brain Activation
Technology

Keywords

  • 11C-PBR28
  • Chronic pain
  • Glia
  • neuroinflammation
  • Translocator protein (18kDa)
  • TSPO

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Loggia, M. L., Chonde, D. B., Akeju, O., Arabasz, G., Catana, C., Edwards, R. R., ... Hooker, J. M. (2015). Evidence for brain glial activation in chronic pain patients. Brain, 138(3), 604-615. https://doi.org/10.1093/brain/awu377

Evidence for brain glial activation in chronic pain patients. / Loggia, Marco L.; Chonde, Daniel B.; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R.; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru Rong; Riley, Misha; Wasan, Ajay D.; Zurcher, Nicole R.; Albrecht, Daniel S.; Vangel, Mark G.; Rosen, Bruce R.; Napadow, Vitaly; Hooker, Jacob M.

In: Brain, Vol. 138, No. 3, 2015, p. 604-615.

Research output: Contribution to journalArticle

Loggia, ML, Chonde, DB, Akeju, O, Arabasz, G, Catana, C, Edwards, RR, Hill, E, Hsu, S, Izquierdo-Garcia, D, Ji, RR, Riley, M, Wasan, AD, Zurcher, NR, Albrecht, DS, Vangel, MG, Rosen, BR, Napadow, V & Hooker, JM 2015, 'Evidence for brain glial activation in chronic pain patients', Brain, vol. 138, no. 3, pp. 604-615. https://doi.org/10.1093/brain/awu377
Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR et al. Evidence for brain glial activation in chronic pain patients. Brain. 2015;138(3):604-615. https://doi.org/10.1093/brain/awu377
Loggia, Marco L. ; Chonde, Daniel B. ; Akeju, Oluwaseun ; Arabasz, Grae ; Catana, Ciprian ; Edwards, Robert R. ; Hill, Elena ; Hsu, Shirley ; Izquierdo-Garcia, David ; Ji, Ru Rong ; Riley, Misha ; Wasan, Ajay D. ; Zurcher, Nicole R. ; Albrecht, Daniel S. ; Vangel, Mark G. ; Rosen, Bruce R. ; Napadow, Vitaly ; Hooker, Jacob M. / Evidence for brain glial activation in chronic pain patients. In: Brain. 2015 ; Vol. 138, No. 3. pp. 604-615.
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