Objective Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS). Design A mixed between/within-subjects longitudinal cohort design. Setting A single academic medical center. Subjects Osteoarthritis patients (n = 91; 62.6% female) undergoing unilateral TKA. Methods We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA. Results Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (p’s<0.05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (p’s<0.05). Bootstrapped mediation analyses revealed significant (p’s<0.05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (p’s<0.05) on post-TKA outcomes that were independent of OS mechanisms. Conclusions Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS.

中文翻译：

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氧化应激介导全膝关节置换术后 6 个月术前心理社会表型与疼痛相关结果之间的关联：一项纵向队列研究

目的 术前更严重的抑郁、焦虑和疼痛灾难化与全膝关节置换术 (TKA) 后更严重的长期疼痛相关。在对先前报道的数据进行二次分析时，我们测试了这些关联是由氧化应激（OS）介导的假设。设计 受试者间/受试者内混合纵向队列设计。设置单一学术医疗中心。受试者接受单侧 TKA 的骨关节炎患者（n = 91；62.6% 女性）。方法 我们在术前评估了抑郁、焦虑和灾难化以及中枢敏化标志物（广泛的疼痛、疼痛的时间总和）。然后在术中放置止血带之前立即获取血样，以量化全身 OS、F2-异前列腺素和异呋喃的体内生物标志物。TKA 后 6 个月评估 TKA 后疼痛强度（最严重疼痛数字评定量表 [NRS]、麦吉尔疼痛问卷 2 [MPQ-2]）和功能（PROMIS 疼痛干扰）。结果术前更大的抑郁、灾难性和广泛的疼痛与更高的术中总生存期（F2-异前列烷+异呋喃/2）相关，这反过来又与更高的全膝关节置换术后疼痛强度和更差的功能相关（p<0.05）。除焦虑外，所有术前表型预测因子均与 TKA 后疼痛和/或功能呈正相关（p＜0.05）。Bootstrapped 中介分析揭示了抑郁（NRS 最严重疼痛、MPQ-2、PROMIS 疼痛干扰）、焦虑（MPQ-2、PROMIS 疼痛干扰）和灾难化（PROMIS 疼痛干扰）对患者的显着（p's<0.05）间接（介导）影响。由于 OS 升高而导致 TKA 后长期不良结果。中枢敏化相关预测因子仅对 TKA 后结果产生直接影响（p<0.05），且与 OS 机制无关。结论 结果表明，抑郁、焦虑和疼痛灾难化对 TKA 后疼痛和功能结果的不利影响部分是由 OS 升高介导的。