神经炎症的代谢物与脊髓损伤后的神经性疼痛有关。
Metabolites of neuroinflammation relate to neuropathic pain after spinal cord injury.
机构信息
From the Spinal Cord Injury Center (D.P., E.H., A.C., P.F.), Balgrist University Hospital, University of Zurich; Institute for Biomedical Engineering (A.H., P.O.W.), University and ETH, Zurich; Department of Radiology (P.O.W.), Swiss Paraplegic Centre, Nottwil, Switzerland; Max Planck Institute for Biological Cybernetics (P.O.W., A.H.), Tuebingen, Germany; Advanced Imaging Research Center (A.H.), UT Southwestern Medical Center, Dallas TX; Department of Brain Repair and Rehabilitation (P.F.) and Wellcome Trust Centre for Neuroimaging (P.F.), UCL Institute of Neurology, University College London, UK; and Department of Neurophysics (P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
出版信息
Neurology. 2020 Aug 18;95(7):e805-e814. doi: 10.1212/WNL.0000000000010003. Epub 2020 Jun 26.
OBJECTIVE
To determine whether cervical cord levels of metabolites are associated with pain sensation after spinal cord injury (SCI) by performing magnetic resonance spectroscopy in patients with SCI with and without neuropathic pain (NP).
METHODS
Cervical cord single-voxel spectroscopic data of 24 patients with SCI (14 with NP, 10 pain-free) and 21 healthy controls were acquired at C2/3 to investigate metabolite ratios associated with neuroinflammation (choline-containing compounds to myoinositol [tCho/mI]) and neurodegeneration (total N-acetylaspartate to myo-inositol [tNAA/mI]). NP levels were measured, and Spearman correlation tests assessed associations between metabolite levels, cord atrophy, and pinprick score.
RESULTS
In patients with NP, tCho/mI levels were increased ( = 0.024) compared to pain-free patients and negatively related to cord atrophy ( = 0.006, = 0.714). Better pinprick score was associated with higher tCho/mI levels ( = 0.032, = 0.574). In pain-free patients, tCho/mI levels were not related to cord atrophy ( = 0.881, = 0.055) or pinprick score ( = 0.676, = 0.152). tNAA/mI levels were similar in both patient groups ( = 0.396) and were not associated with pinprick score in patients with NP ( = 0.405, = 0.242) and pain-free patients ( = 0.117, = 0.527).
CONCLUSIONS
Neuroinflammatory metabolite levels (i.e., tCho/mI) were elevated in patients with NP, its magnitude being associated with less cord atrophy and greater pain sensation (e.g., pinprick score). This suggests that patients with NP have more residual spinal tissue and greater metabolite turnover than pain-free patients. Neurodegenerative metabolite levels (i.e., tNAA/mI) were associated with greater cord atrophy but unrelated to NP. Identifying the metabolic NP signature provides new NP treatment targets and could improve patient stratification in interventional trials.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that levels of magnetic resonance spectroscopy-identified metabolites of neuroinflammation were elevated in patients with SCI with NP compared to those without NP.
目的
通过对伴有和不伴有神经性疼痛（NP）的脊髓损伤（SCI）患者进行脊髓磁共振波谱分析，确定颈髓代谢物水平与 SCI 后疼痛感觉之间的关系。
方法
在 C2/3 采集 24 例 SCI 患者（14 例伴有 NP，10 例无痛）和 21 例健康对照者的颈髓单体素波谱数据，以研究与神经炎症（胆碱化合物与肌醇[tCho/mI]）和神经退行性变（总 N-乙酰天门冬氨酸与肌醇[tNAA/mI]）相关的代谢物比值。测量 NP 水平，并进行 Spearman 相关检验，以评估代谢物水平、脊髓萎缩和刺痛评分之间的相关性。
结果
与无痛患者相比，NP 患者的 tCho/mI 水平升高（ = 0.024），且与脊髓萎缩呈负相关（ = 0.006， = 0.714）。更好的刺痛评分与更高的 tCho/mI 水平相关（ = 0.032， = 0.574）。在无痛患者中，tCho/mI 水平与脊髓萎缩（ = 0.881， = 0.055）或刺痛评分（ = 0.676， = 0.152）无关。两组患者的 tNAA/mI 水平相似（ = 0.396），NP 患者（ = 0.405， = 0.242）和无痛患者（ = 0.117， = 0.527）的 tNAA/mI 水平与刺痛评分均无关。
结论
NP 患者的神经炎症代谢物水平（即 tCho/mI）升高，其程度与脊髓萎缩程度较小和疼痛感觉较大（例如刺痛评分）相关。这表明 NP 患者比无痛患者具有更多的残留脊髓组织和更大的代谢物周转率。神经退行性代谢物水平（即 tNAA/mI）与脊髓萎缩程度相关，但与 NP 无关。确定磁共振波谱鉴定的代谢物 NP 特征提供了新的 NP 治疗靶点，并可改善介入性试验中的患者分层。
证据分类
本研究提供了 II 级证据，表明伴有 NP 的 SCI 患者的磁共振波谱分析确定的神经炎症代谢物水平高于不伴有 NP 的患者。
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