Tappe Alix, Burzynski Emily, Patel Jhanvi, Cheyne Ithamar, Mikaszewska-Sokolewicz Małgorzata
Anesthesiology and Intensive Care Scientific Circle English Division (ANKONA ED), Medical University of Warsaw, 02-091 Warsaw, Poland.
Department of Anesthesiology and Intensive Care, Children's Memorial Health Institute, 04-736 Warsaw, Poland.
Reports (MDPI). 2025 Aug 22;8(3):156. doi: 10.3390/reports8030156.
Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use.
A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit.
This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine's metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy.
Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care.
截肢后疼痛（PAP）是一个统称，包括残肢痛（RLP）和幻肢痛（PLP），对肢体缺失后的恢复和生活质量构成重大挑战。氯胺酮作为一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，因其在治疗PAP方面的潜力，尤其是在难治性病例中的潜力而受到关注。本叙述性综述探讨了氯胺酮治疗PAP的疗效以及药物基因组学在指导其使用方面的新兴作用。
对PubMed、Embase和Cochrane数据库进行文献综述，重点关注临床试验、系统评价以及基因对氯胺酮代谢和反应的影响。研究表明，围手术期使用氯胺酮可降低PAP的严重程度并减少阿片类药物的使用。然而，结果各不相同，一些患者经历短暂缓解，而另一些患者则获得长期益处。
这种变异性可能与CYP2B6、CYP3A4/5、儿茶酚-O-甲基转移酶（COMT）Val158Met、溶质载体家族6成员2（SLC6A2）和钾通道亚家族S成员1（KCNS1）的基因差异有关，这些基因会影响氯胺酮的代谢、疗效和副作用情况。了解这些药物基因组学因素可以实现更个性化、有效的氯胺酮治疗。
尽管氯胺酮前景广阔，但给药方案不一致以及基因数据整合有限阻碍了标准化。对基因型指导的氯胺酮方案的进一步研究可能会改善治疗结果，并为截肢者护理中的精准镇痛提供支持。
