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.

The immune response of the human brain to abdominal surgery

“…Another caveat in interpreting our results is the possibility that postoperative pain may have an effect on TSPO binding. As far as we know, only 1 published study has investigated this issue, showing a relative increase in [ 11 C]PBR28 binding in thalamus of patients with chronic pain 51 ; it should be noted that this study reported relative changes in regional radioligand uptake and failed to describe any global difference between patients. In the present study, patients did not report GM 5 gray matter; HIP 5 hippocampus; LFC 5 lateral frontal cortex; V T 5 distribution volume.…”

“…30,50 Potential methodological sources of variance include the use of a metabolite-corrected plasma input that may introduce measurement errors, for instance due to the high rate of radioligand metabolism. To reduce the impact of this source of variability, simplified methods of quantification have been proposed, such as calculating standardized uptake values or V T , which are then normalized to whole brain, 51,52 or pseudoreference regions such as the cerebellum. 53 However, these approaches will render only relative rather than absolute differences or changes and thus require a hypothesis that only specific regions of the brain are affected, which may not be the case even in disorders with a presumed circumscribed pathology.…”

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

“…Besides signs of neuroinflammation as reflected by CSF cytokine indices, brain positron emission tomography (PET) scans of patients with chronic back pain show microglial cell specific activation (greater than healthy controls) in: 1) medial thalamic, 2) post central gyrus, and 3) paracentral lobule, suggesting that chronic pain mediated neuroinflammation and central sensitization likely co-occur in both the brain and spinal cord (Loggia et al, 2015). The mechanisms of central sensitization are known to involve neuronal interaction with activated glia cells and astrocytes (Milligan and Watkins, 2009;Watkins and Maier, 2005).…”

Chronic Back Pain: From Pathogenetic Concepts to Therapeutic Strategies

“…В случае дискогенной острой боли в спине провоспалительные агенты, ассоциированные с дегенерацией дисков, сенсибилизируя ноцицепторы, могут выступать в качестве активатора микроглии. Совсем недавно с помощью функциональной нейровизуализа-ции было показано, что маркеры глиальной активации (белки-транслокаторы) были значительно выше у пациен-тов с хроническими болями в спине по сравнению с контрольной группой -в таламической зоне, связанной с начальными процессами оценки болевых стимулов [13].…”