Evidence for brain glial activation in chronic pain patients
Evidence for brain glial activation in chronic pain patients
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DOI：
10.1093/brain/awu377
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发表时间：
2015-03-01
期刊：
影响因子：
14.5
通讯作者：
Hooker, Jacob M.
中科院分区：
文献类型：
--
作者：
Loggia, Marco L.;Chonde, Daniel B.;Hooker, Jacob M.
尽管大量证据表明小胶质细胞和星形胶质细胞在动物模型中持续疼痛的建立和维持中起关键作用，但神经胶质细胞在人类疼痛障碍中的作用尚不清楚。在这里，使用集成正电子发射断层扫描-磁共振成像的新技术和最近开发的放射性配基C-11-PBR28，我们显示了慢性下腰痛患者大脑中神经胶质激活的标志-移位器蛋白(TSPO)的水平增加。由于TSPO基因的Ala147Thr多态影响与C-11-PBR28的结合亲和力，因此从筛选和基因分型的更大样本中确定了9对患者-对照，并进行了配对设计，其中每个患者与TSPO多态、年龄和性别匹配的对照受试者相匹配(7例ALA/ALA和2例ALA/Thr，每组5名男性和4名女性；年龄中位数相差：1岁；年龄范围：29-63岁和28-65岁)。归一化为全脑的标准化摄取值在多个大脑区域，包括丘脑和推定的腰椎和腿部的躯体感觉表征，患者组显著高于对照组。丘脑TSPO水平与临床疼痛和循环中促炎症因子IL-6的水平呈负相关，表明TSPO的表达在人类中具有疼痛保护/抗炎作用，正如动物研究所预测的那样。考虑到激活的胶质细胞在持续性疼痛的建立和/或维持中的假定作用，本研究结果提供了临床意义，可能有助于指导未来对各种持续性疼痛状况的病理生理学和治疗的研究。
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 C-11-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 C-11-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.