Astudy on Opioid-Reducing Effect of NMDA Receptor Antagonists as Analgesics

背景：辅助镇痛药是指通常不作为止痛药使用，但对特殊疼痛（如神经性疼痛）有镇痛作用的镇痛药。大约30%的癌症患者患有神经性疼痛，这在很大程度上造成了治疗困难。此外，根据疼痛程度使用阿片类镇痛药似乎对80%以上的癌症疼痛病例有效。然而，在大约5%的患者中，由于嗜睡、恶心和便秘等不良反应，似乎不能根据疼痛程度增加阿片类药物的剂量。既往研究报道了阿片类镇痛药与辅助镇痛药对神经性疼痛的协同或加性作用，但在正常躯体痛中，辅助镇痛药对阿片类镇痛的增强作用尚未见报道。目的与方法本研究旨在探讨阿片类药物有效的躯体疼痛是否可以通过同时使用辅助镇痛药（NMDA受体拮抗剂、抗抑郁药、抗惊厥药等药物）来减少阿片类药物的剂量。结果：在研究期间，有几种情况导致目标药物清单发生变化，氯胺酮意外被指定为麻醉药物，加巴喷丁被批准使用为抗惊厥药。因此，每种药物的病例数很少，当时无法进行统计分析。然而，相当多的患者表现出阿片类药物的减少作用。我们认为这一结果为进一步的研究提供了依据。讨论：本研究发现，当阿片类药物如阿片类不耐受等不良反应难以治疗时，添加辅助镇痛药以及改变阿片类药物的类型可能会改善疼痛管理不足的情况。同时，本研究对癌症姑息治疗的实践也有一定的价值。

Background: Adjuvant analgesics are described as the drugs used as analgesics which are not usually used as painkiller but have analgesic effect on special pain (e.g. neuropathic pain). Approximately 30% of patients with cancer suffer from neuropathic pain, which contributes largely to the treatment difficulties Additionally, use of opioid analgesics based on degree of pain appears to be effective in over 80% cases with cancer pain. However, in approximately 5% of patients, it seems that the dose of opioids cannot be increased based on degree of pain because of the adverse effects such as drowsiness, nausea and constipation. Previous studies have reported the synergistic or additive effect of opioid and adjuvant analgesics on neuropathic pain, but enhancing effect of adjuvant analgesics on opioid analgesia in normal somatic pain has not been reported.Objective and Methods The objective of this study is to investigate whether the dose of opioid can be reduced in opioid-effective somatic pain by concomitant use of adjuvant analgesics (NMDA receptor antagonists, antidepressants, anticonvulsants and other drugs).Results: There were several situations which cause change in the list of target drugs, ketamine was unexpectedly designated as narcotic drug and use of gabapentin as anticonvulsant agent was approved during the study period. Therefore, the number of cases for each drug was few and statistical analysis was impossible at that time. However, considerable number of patients showed opioid-reducing effect of adjuvant analgesics. We considered that this result provided basis on further investigation.Discussion: This study found the possibility that the addition of adjuvant analgesics, as well as changing the type of opioid, may improve insufficient pain management when it is difficult due to untreatable adverse effects of opioid like opioid-intolerance. Also, this study was valuable from the viewpoint of contribution to the palliative care practice in cancer.