Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain.
Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain.
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DOI：
10.1097/j.pain.0000000000002480
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发表时间：
2022-06-01
期刊：
影响因子：
7.4
通讯作者：
Williams SCR
中科院分区：
文献类型：
--
作者：
Martins D;Dipasquale O;Veronese M;Turkheimer F;Loggia ML;McMahon S;Howard MA;Williams SCR
补充数字内容可在正文中找到。成像转录学将基因、细胞类别和生物途径与皮质形态重构慢性疼痛的体内成像相关连接起来。慢性疼痛是一种非常虚弱和难以治疗的疾病，它会影响大脑的结构。虽然慢性疼痛的发展是适度遗传的，但微观遗传结构中与疾病相关的变化如何驱动宏观大脑异常目前基本上是未知的。在这里，我们检测了形态相似性(MS)的变化，并应用综合成像转录组学方法来确定这些MS变化的转录和细胞相关性，在3个独立的小队列患者中，这些患者患有不同的慢性疼痛综合征(膝骨性关节炎、下腰痛和纤维肌痛)，以及年龄匹配和性别匹配的无痛对照组。我们发现了一种新的皮质MS重塑模式，主要涉及岛叶和边缘皮质中的中小MS增加(这些变化都没有在严格的错误发现率校正中存活下来)。这种变化模式与在严重抑郁症患者中观察到的不同，并跨越了特定疼痛综合征的界限。通过利用Allen人脑图谱的转录数据，我们发现慢性疼痛中皮质MS的重塑在空间上与疼痛相关基因的全脑表达相关，并广泛参与神经胶质免疫反应和神经元可塑性。我们的发现将基因、细胞类别和生物路径与慢性疼痛的活体成像相关水平联系起来。虽然相互关联，但我们的数据表明，慢性疼痛中的皮质重塑可能由大脑细胞结构的多个元素塑造，并确定了几条可能在未来的遗传关联或药物开发研究中优先考虑的途径。
Supplemental Digital Content is Available in the Text. Imaging transcriptomics bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of cortical morphometric remodelling chronic pain. Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. Although the development of chronic pain is moderately heritable, how disease-related alterations at the microscopic genetic architecture drive macroscopic brain abnormalities is currently largely unknown. Here, we examined alterations in morphometric similarity (MS) and applied an integrative imaging transcriptomics approach to identify transcriptional and cellular correlates of these MS changes, in 3 independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain, and fibromyalgia) and age-matched and sex-matched pain-free controls. We uncover a novel pattern of cortical MS remodelling involving mostly small-to-medium MS increases in the insula and limbic cortex (none of these changes survived stringent false discovery rate correction for the number of regions tested). This pattern of changes is different from that observed in patients with major depression and cuts across the boundaries of specific pain syndromes. By leveraging transcriptomic data from Allen Human Brain Atlas, we show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes related to pain and broadly involved in the glial immune response and neuronal plasticity. Our findings bridge levels to connect genes, cell classes, and biological pathways to in vivo imaging correlates of chronic pain. Although correlational, our data suggest that cortical remodelling in chronic pain might be shaped by multiple elements of the cellular architecture of the brain and identifies several pathways that could be prioritized in future genetic association or drug development studies.
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影响因子：
3.7
作者：
Baliki MN;Mansour AR;Baria AT;Apkarian AV
通讯作者：
Apkarian AV
影响因子：
2.5
作者：
Farmer MA;Baliki MN;Apkarian AV
通讯作者：
Apkarian AV
DOI：
10.1016/j.bbi.2018.09.018
发表时间：
2019-01
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Albrecht DS;Forsberg A;Sandström A;Bergan C;Kadetoff D;Protsenko E;Lampa J;Lee YC;Höglund CO;Catana C;Cervenka S;Akeju O;Lekander M;Cohen G;Halldin C;Taylor N;Kim M;Hooker JM;Edwards RR;Napadow V;Kosek E;Loggia ML
通讯作者：
Loggia ML
影响因子：
34.7
作者：
Alexander-Bloch, Aaron;Giedd, Jay N.;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.
DOI：
10.1523/jneurosci.3554-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alexander-Bloch A;Raznahan A;Bullmore E;Giedd J
通讯作者：
Giedd J