Lossignol Dominique A, Obiols-Portis Myriam, Body Jean-Jacques
Institut Jules Bordet, Clinique des Soins Supportifs et des Soins Palliatifs, Service de médecine interne, Université Libre de Bruxelles, 1 Rue Héger Bordet, 1000, Brussels, Belgium.
Support Care Cancer. 2005 Mar;13(3):188-93. doi: 10.1007/s00520-004-0684-4. Epub 2004 Oct 6.
GOALS AND WORK: Despite medical awareness, intractable pain is a serious problem in cancer and occurs in up to 2% of advanced cancer patients. However, few data are available concerning the optimal treatment of such patients. The emergence of intractable pain may notably be due to the activation of N-methyl-D-aspartate (NMDA) receptors located in the central nervous system. NMDA antagonists might thus be an interesting approach in such pain syndromes.
Twelve patients with intractable cancer pain received a test dose of 5-10 mg of ketamine, a strong NMDA antagonist, in order to determine their response and tolerance to the drug. Continuous intravenous infusions of ketamine associated with morphine were then administered.
The acute test dose was successful in all cases (VAS <3/10 after 5 min). The prolonged use of ketamine allowed us to reduce the total daily dose of morphine required (range: 200-1,200 mg) by 50% and allowed eight patients to go home with a portable pump with morphine and ketamine during a relatively long period of time (range: 7-350 days, median: 58 days). Side effects were moderate (dizziness) and they were limited to the test phase.
Our data suggest the importance of NMDA receptors in the genesis of chronic cancer pain and indicate that NMDA antagonists should be further studied for the management of cancer pain and, in particular, intractable pain.
目标与工作：尽管医学上已有认识，但顽固性疼痛仍是癌症中的一个严重问题，在高达2%的晚期癌症患者中出现。然而，关于此类患者的最佳治疗方法，可用数据很少。顽固性疼痛的出现可能尤其归因于位于中枢神经系统的N-甲基-D-天冬氨酸（NMDA）受体的激活。因此，NMDA拮抗剂可能是治疗此类疼痛综合征的一种有意义的方法。
12名患有顽固性癌症疼痛的患者接受了5-10毫克氯胺酮（一种强效NMDA拮抗剂）的试验剂量，以确定他们对该药物的反应和耐受性。然后给予与吗啡联合的氯胺酮持续静脉输注。
急性试验剂量在所有病例中均成功（5分钟后视觉模拟评分法[VAS]<3/10）。氯胺酮的长期使用使我们能够将所需吗啡的每日总剂量（范围：200-1200毫克）减少50%，并使8名患者在较长一段时间内（范围：7-350天，中位数：58天）带着便携式吗啡和氯胺酮泵回家。副作用较轻（头晕），且仅限于试验阶段。
我们的数据表明NMDA受体在慢性癌症疼痛发生中的重要性，并表明NMDA拮抗剂应进一步研究用于癌症疼痛尤其是顽固性疼痛的管理。
