Weerasekera Akila, Morrissey Erin, Kim Minhae, Saha Atreyi, Lin Yang, Alshelh Zeynab, Torrado-Carvajal Angel, Albrecht Daniel, Akeju Oluwaseun, Kwon Young-Min, Bedair Hany, Chen Antonia F, Napadow Vitaly, Schreiber Kristin, Ratai Eva-Maria, Edwards Robert R, Loggia Marco L
Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Medical Image Analysis and Biometry Laboratory, Universidad Rey Juan Carlos, Madrid, Spain.
Pain. 2021 Jul 1;162(7):2014-2023. doi: 10.1097/j.pain.0000000000002198.
The weak association between disability levels and "peripheral" (ie, knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in patients with KOA, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four presurgical patients with KOA and 13 healthy controls were scanned using a PRESS sequence (TE = 30 ms, TR = 1.7 seconds, voxel size = 15 × 15 × 15 mm). In addition, 13 patients were rescanned 4.1 ± 1.6 (mean ± SD) weeks post-TKA. When using creatine (Cr)-normalized levels, presurgical KOA patients demonstrated lower N-acetylaspartate (NAA) (P < 0.001), higher myoinositol (mIns) (P < 0.001), and lower Choline (Cho) (P < 0.05) than healthy controls. The mIns levels were positively correlated with pain severity scores (r = 0.37, P < 0.05). These effects reached statistical significance also using water-referenced concentrations, except for the Cho group differences (P ≥ 0.067). Post-TKA patients demonstrated an increase in NAA (P < 0.01), which returned to the levels of healthy controls (P > 0.05), irrespective of metric. In addition, patients demonstrated postsurgical increases in Cr-normalized (P < 0.001), but not water-referenced mIns, which were proportional to the NAA/Cr increases (r = 0.61, P < 0.05). Because mIns is commonly regarded as a glial marker, our results are suggestive of a possible dual role for neuroinflammation in KOA pain and post-TKA recovery. Moreover, the apparent postsurgical normalization of NAA, a putative marker of neuronal integrity, might implicate mitochondrial dysfunction, rather than neurodegenerative processes, as a plausible pathophysiological mechanism in KOA. More broadly, our results add to a growing body of literature suggesting that some pain-related brain alterations can be reversed after peripheral surgical treatment.
残疾程度与“外周”（即膝盖）检查结果之间的弱关联表明，中枢神经系统改变可能在膝关节骨关节炎（KOA）的病理生理学中起作用。在此，我们使用氢质子磁共振波谱（1H-MRS）评估了全膝关节置换术（TKA）前后KOA患者的脑代谢物改变。34例TKA术前KOA患者和13名健康对照者接受了PRESS序列扫描（TE = 30 ms，TR = 1.7秒，体素大小 = 15×15×15 mm）。此外，13例患者在TKA术后4.1±1.6（均值±标准差）周时再次接受扫描。当使用肌酸（Cr）标准化水平时，TKA术前KOA患者与健康对照者相比，N-乙酰天门冬氨酸（NAA）水平较低（P < 0.001），肌醇（mIns）水平较高（P < 0.001），胆碱（Cho）水平较低（P < 0.05）。mIns水平与疼痛严重程度评分呈正相关（r = 0.37，P < 0.05）。除了Cho组差异外（P≥0.067），使用水参照浓度时这些效应也具有统计学意义。TKA术后患者的NAA增加（P < 0.01），无论采用何种测量指标，其均恢复至健康对照者水平（P > 0.05）。此外，患者术后Cr标准化的mIns增加（P < 0.001），但水参照的mIns未增加，且与NAA/Cr的增加成比例（r = 0.61，P < 0.05）。由于mIns通常被视为一种胶质细胞标志物，我们的结果提示神经炎症在KOA疼痛和TKA术后恢复中可能具有双重作用。此外，作为神经元完整性的一种假定标志物，NAA在术后明显恢复正常，这可能意味着线粒体功能障碍而非神经退行性过程是KOA中一种合理的病理生理机制。更广泛地说，我们的结果进一步丰富了越来越多的文献，表明一些与疼痛相关的脑改变在外周手术治疗后可以逆转。
