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: 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 Zürcher, Daniel S Albrecht, Mark G Vangel, Bruce R Rosen, Vitaly Napadow, Jacob M Hooker
• Journal: Brain : a journal of neurology (Brain) Vol. 138 Issue Pt 3 Pg. 604-15 (Mar 2015) ISSN: 1460-2156 [Electronic] England
• PMID: 25582579 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
• Interleukin-6
• Pyrimidines
• Receptors, GABA
• TSPO protein, human

Topics

• Adult
• Aged
• Brain (diagnostic imaging, metabolism, pathology)
• Case-Control Studies
• Chronic Pain (diagnostic imaging, genetics, pathology)
• Female
• Genotype
• Humans
• Interleukin-6 (blood)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neuroglia (diagnostic imaging, pathology)
• Polymorphism, Single Nucleotide (genetics)
• Positron-Emission Tomography
• Pyrimidines
• Receptors, GABA (genetics, metabolism)
• Statistics as Topic