Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital Boston, MA, United States.
Pain. 2022 Jun 1;163(6):e759-e773. doi: 10.1097/j.pain.0000000000002480. Epub 2021 Sep 23.
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.
慢性疼痛是一种高度衰弱且难以治疗的疾病，会影响大脑结构。尽管慢性疼痛的发展具有中等程度的遗传性，但目前尚不清楚与疾病相关的微观遗传结构变化如何驱动宏观大脑异常。在这里，我们检查了形态相似性（MS）的变化，并应用了综合影像学转录组学方法来识别这些 MS 变化的转录和细胞相关性，在 3 个独立的小队列中，这些队列包括具有不同慢性疼痛综合征（膝骨关节炎、下腰痛和纤维肌痛）的患者和年龄匹配及性别匹配的无痛对照者。我们发现了一种新的皮质 MS 重塑模式，涉及岛叶和边缘皮质的中小 MS 增加（这些变化中没有一个在经过严格的错误发现率校正后，在测试的区域数量上幸存下来）。这种变化模式与在患有重度抑郁症的患者中观察到的不同，并跨越了特定疼痛综合征的界限。通过利用来自艾伦人类大脑图谱的转录组数据，我们表明慢性疼痛中的皮质 MS 重塑与大脑中与疼痛相关的基因的广泛表达以及广泛涉及神经胶质免疫反应和神经元可塑性的基因空间相关。我们的研究结果连接了基因、细胞类型和生物途径与慢性疼痛的体内成像相关性。尽管具有相关性，但我们的数据表明，慢性疼痛中的皮质重塑可能受到大脑细胞结构的多个因素的影响，并确定了几个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。
