Chronic pain is a highly debilitating and difficult to treat condition, which affects the structure of the brain. While 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 three independent small cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain and fibromyalgia) and age 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 FDR 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 suggests 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.

中文翻译：

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慢性疼痛中皮质形态重塑的转录和细胞特征。

慢性疼痛是一种使人高度衰弱且难以治疗的疾病，它会影响大脑的结构。虽然慢性疼痛的发展具有一定程度的遗传性，但与疾病相关的微观遗传结构的改变如何驱动宏观的大脑异常目前在很大程度上尚不清楚。在这里，我们检查了形态相似性（MS）的变化，并应用综合成像转录组学方法来识别这些 MS 变化的转录和细胞相关性，在三个独立的小队列中患有不同的慢性疼痛综合征（膝骨关节炎、腰痛和纤维肌痛）的患者中）以及年龄和性别匹配的无痛对照。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的小到中度 MS 增加（这些变化都没有经过对测试区域数量的严格 FDR 校正）。这种变化模式与在重度抑郁症患者中观察到的变化模式不同，并且跨越了特定疼痛综合征的界限。通过利用艾伦人脑图谱的转录组数据，我们发现慢性疼痛中的皮质 MS 重塑与疼痛相关基因的全脑表达空间相关，并广泛参与神经胶质免疫反应和神经元可塑性。我们的研究结果将基因、细胞类别和生物途径与慢性疼痛的体内成像相关性联系起来。尽管相关，但我们的数据表明，慢性疼痛的皮质重塑可能是由大脑细胞结构的多个元素决定的，并确定了在未来的遗传关联或药物开发研究中可以优先考虑的几个途径。