Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Gibbon Building, 8290, Philadelphia, PA, 19107, USA.
Psychiatry & Pediatrics, Cooper Medical School of Rowan University, Camden, NJ, USA.
Curr Pain Headache Rep. 2021 Jul 16;25(9):57. doi: 10.1007/s11916-021-00977-w.
While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented.
Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.
虽然氯胺酮的镇痛作用主要归因于 N-甲基-D-天冬氨酸受体的拮抗作用，但有证据表明，其抗抑郁和可能的镇痛活性还涉及多种其他途径。本文讨论了这些机制以及氯胺酮在神经病理性疼痛范式中的作用。动物研究表明氯胺酮具有神经毒性，但这种毒性在人类中的可转化性尚不清楚，本文同时介绍了关键的啮齿动物和人体研究结果。
氯胺酮的代谢物，特别是（2R,6R）-羟基去甲氯胺酮，可能比以前认为的在其临床活性中发挥更大的作用。氯胺酮对 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和雷帕霉素靶蛋白的激活是仍在阐明的机制。氯胺酮可能在涉及疼痛处理改变的神经病理性疼痛中效果最佳。虽然人们对氯胺酮了解很多，但新的研究将继续确定其在临床医学中的作用。缺乏支持氯胺酮在人类中具有神经毒性的证据，不应阻碍未来的氯胺酮临床试验。
