Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain.
Eur J Pain. 2021 Oct;25(9):2050-2064. doi: 10.1002/ejp.1820. Epub 2021 Jun 22.
Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood.
We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87).
Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus.
These findings support single voxel placement targeting nociceptive processing areas in prior H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia.
This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self-referential cognitive processing area as well as pain-processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians.
纤维肌痛是一种集中的多维慢性疼痛综合征，但它的病理生理学尚未完全了解。
我们应用了 3D 磁共振波谱成像（MRSI），覆盖了多个皮质和皮质下脑区，以研究神经代谢物（例如谷氨酸和谷氨酰胺的组合，Glx；肌醇，mIno；以及组合的（总）N-乙酰天冬氨酸和 N-乙酰天门冬氨酸谷氨酸，tNAA）水平与纤维肌痛女性多维临床/行为变量（例如疼痛灾难化，临床疼痛严重程度和诱发疼痛敏感性）之间的关联（N=87）。
疼痛灾难化评分与岛叶皮层中的 Glx 和 tNAA 水平呈正相关，与后扣带回皮层（PCC）中的 mIno 水平呈负相关。临床疼痛严重程度与岛叶和 PCC 中的 Glx 水平呈正相关，与前中扣带回皮层（aMCC）中的 tNAA 水平呈正相关，但与 aMCC 和丘脑中的 mIno 水平呈负相关。诱发疼痛敏感性与岛叶皮层、MCC、PCC 和丘脑中的 tNAA 水平呈负相关。
这些发现支持先前 H-MRS 研究中针对伤害感受处理区域的单体素放置，但也突出了其他不常作为目标的区域，例如 PCC，作为慢性疼痛病理生理学的重要区域。确定与纤维肌痛多维症状相关的靶脑区（例如对疼痛的消极认知/情感反应、临床疼痛、诱发疼痛敏感性）可能有助于开发神经调节和个体化治疗方法。此外，3D MRSI 的高效多区域采样可以减少冗长的扫描时间，从而减轻基于分子的大脑机制在纤维肌痛多维方面的临床研究应用的负担。
这项大规模 N 研究将纤维肌痛患者的大脑代谢物与疼痛特征联系起来，具有更好的空间分辨率和脑覆盖范围，以了解疼痛灾难化和疼痛传递其他方面的潜在分子机制。自我参照认知处理区域以及疼痛处理区域中的代谢物水平与疼痛结果相关。这些结果可以帮助理解其病理生理学和为临床医生提供治疗策略。
