Medical Physics Department, Medical School, University of Thessaly, Larisa, Greece.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Hum Brain Mapp. 2022 Dec 1;43(17):5235-5249. doi: 10.1002/hbm.25999. Epub 2022 Jul 7.
Arterial spin labelling (ASL) plays an increasingly important role in neuroimaging pain research but does not provide molecular insights regarding how regional cerebral blood flow (rCBF) relates to underlying neurotransmission. Here, we integrate ASL with positron emission tomography (PET) and brain transcriptome data to investigate the molecular substrates of rCBF underlying clinically relevant pain states. Two data sets, representing acute and chronic ongoing pain respectively, were utilised to quantify changes in rCBF; one examining pre-surgical versus post-surgical pain, and the second comparing patients with painful hand Osteoarthritis to a group of matched controls. We implemented a whole-brain spatial correlation analysis to explore associations between change in rCBF (ΔCBF) and neurotransmitter receptor distributions derived from normative PET templates. Additionally, we utilised transcriptomic data from the Allen Brain Atlas to inform distributions of receptor expression. Both datasets presented significant correlations of ΔCBF with the μ-opioid and dopamine-D2 receptor expressions, which play fundamental roles in brain activity associated with pain experiences. ΔCBF also correlated with the gene expression distributions of several receptors involved in pain processing. Overall, this is the first study illustrating the molecular basis of ongoing pain ASL indices and emphasises the potential of rCBF as a biomarker in pain research.
动脉自旋标记（ASL）在神经影像学疼痛研究中发挥着越来越重要的作用，但它不能提供关于区域脑血流（rCBF）与潜在神经传递之间关系的分子见解。在这里，我们将 ASL 与正电子发射断层扫描（PET）和大脑转录组数据相结合，研究与临床相关疼痛状态相关的 rCBF 的分子基础。使用两个数据集分别代表急性和慢性持续疼痛，以量化 rCBF 的变化；一个检查手术前后的疼痛，另一个将患有手部骨关节炎疼痛的患者与一组匹配的对照组进行比较。我们实施了全脑空间相关分析，以探索 rCBF 变化（ΔCBF）与来自规范 PET 模板的神经递质受体分布之间的关联。此外，我们利用艾伦大脑图谱的转录组数据来告知受体表达的分布。两个数据集都呈现了ΔCBF 与 μ-阿片受体和多巴胺-D2 受体表达的显著相关性，这些受体在与疼痛体验相关的大脑活动中起着至关重要的作用。ΔCBF 还与涉及疼痛处理的几个受体的基因表达分布相关。总的来说，这是第一项阐明持续疼痛 ASL 指数的分子基础的研究，并强调了 rCBF 作为疼痛研究中生物标志物的潜力。
