Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Department of Nursing, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Anaesth Crit Care Pain Med. 2024 Apr;43(2):101361. doi: 10.1016/j.accpm.2024.101361. Epub 2024 Feb 24.
The Catechol-O-methyltransferase (COMT) gene, responsible for encoding an enzyme crucial in the metabolism of catecholamines, is known to play a significant role in pain perception. Polymorphisms within this gene, particularly the COMT rs4680 genotypes, have been linked to various acute pain phenotypes. This prospective cohort study examines interactions among the genetic polymorphism COMT rs4680 genotypes, preoperative knee pain, and pain catastrophizing in chronic postsurgical pain (CPSP) at 3, 6, and 12 months post-total knee arthroplasty (TKA).
A total of 280 patients undergoing primary unilateral TKA participated, sharing demographic details, preoperative knee pain levels, psychological variables (pain catastrophizing), and COMT rs4680 genotyping via venous blood samples. Telephone interviews at specified intervals enabled the application of binary logistic regressions and interaction models.
Significant influences of preoperative knee pain and pain catastrophizing on postsurgical outcomes were observed. Specifically, at the first time point (T1, 3 months post-TKA), a notable moderation effect was identified in preoperative knee pain (R change = 0.026, p = 0.026). The Johnson-Neyman regions of significance (RoS) indicated these moderation effects were significant above a threshold of 17.18 (p = 0.05), accounting for 26.4%. At the third time point (T3, 12 months post-TKA), a complex three-way interaction among genotypes (GG, GA, and AA carriers) was evident, resulting in an R change of 0.051 (p = 0.009). Here, the RoS for pain catastrophizing was above 32.74 for 30.5% of GG genotype carriers, above 22.38 for 50.8% of GA carriers, and below 11.94 for 63.2% of AA carriers.
This study illuminates the significant role of the COMT Val158Met rs4680 polymorphism in susceptibility to prolonged pain following TKA. It also elucidates how these genetic genotypes interplay with preoperative knee pain and pain catastrophizing. Such intricate genetic-psychological-pain relationships necessitate additional investigation to confirm these findings and potentially guide post-TKA pain management strategies.
儿茶酚-O-甲基转移酶（COMT）基因负责编码儿茶酚胺代谢中至关重要的酶，已知其在疼痛感知中发挥重要作用。该基因内的多态性，特别是 COMT rs4680 基因型，与各种急性疼痛表型有关。这项前瞻性队列研究检查了 COMT rs4680 基因型的遗传多态性、术前膝关节疼痛和疼痛灾难化在全膝关节置换术后 3、6 和 12 个月慢性手术后疼痛（CPSP）中的相互作用。
共有 280 名接受单侧初次 TKA 的患者参与了研究，他们提供了人口统计学资料、术前膝关节疼痛水平、心理变量（疼痛灾难化）和 COMT rs4680 基因型的静脉血样本。在指定的时间间隔进行电话访谈，以应用二元逻辑回归和交互模型。
术前膝关节疼痛和疼痛灾难化对术后结果有显著影响。具体来说，在第一个时间点（T1，TKA 后 3 个月），术前膝关节疼痛存在显著的调节效应（R 变化=0.026，p=0.026）。约翰逊-尼曼显著性区域（RoS）表明，这些调节效应在阈值为 17.18 以上时显著（p=0.05），占 26.4%。在第三个时间点（T3，TKA 后 12 个月），基因型（GG、GA 和 AA 携带者）之间存在复杂的三向相互作用，导致 R 变化为 0.051（p=0.009）。在此，疼痛灾难化的 RoS 对于 30.5%的 GG 基因型携带者高于 32.74，对于 50.8%的 GA 携带者高于 22.38，对于 63.2%的 AA 携带者低于 11.94。
这项研究阐明了 COMT Val158Met rs4680 多态性在 TKA 后长期疼痛易感性中的重要作用。它还阐明了这些基因基因型如何与术前膝关节疼痛和疼痛灾难化相互作用。这种复杂的遗传-心理-疼痛关系需要进一步研究来证实这些发现，并可能指导 TKA 后疼痛管理策略。
