Ketamine and N-acetylaspartylglutamate peptidase inhibitor exert analgesia in bone cancer pain
Ketamine and N-acetylaspartylglutamate peptidase inhibitor exert analgesia in bone cancer pain
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DOI：
10.1007/bf03022832
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发表时间：
2006-09-01
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影响因子：
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通讯作者：
Yamamoto, Tatsuo
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作者：
Saito, Osamu;Aoe, Tomohiko;Yamamoto, Tatsuo
目的：并非所有的骨癌疼痛都可以用现有的治疗方法有效治疗。在本研究中，ip α-2激动剂的作用（右美托咪定和可乐定），N-甲基-D-天冬氨酸（NMDA）拮抗剂（MK-801和氯胺酮）、N-乙酰基谷氨酸肽酶抑制剂（ZJ-43）和吗啡在小鼠骨癌疼痛模型中进行了检查。通过将小鼠肉瘤细胞注射到股骨远端的骨髓腔中来产生骨癌疼痛模型。为了估计骨癌疼痛的水平，对通过将von Frey单丝（0.166 g）重复应用于肿瘤细胞植入部位诱导的疼痛相关行为的数量进行计数。结果：吗啡组术后镇痛效果显著（P < 0.001）。α-2激动剂产生镇痛作用（P < 0.001），其疗效与吗啡相似，但仅在产生严重镇静的剂量下。MK-801仅具有有限的镇痛作用，而氯胺酮产生与吗啡相同的镇痛作用（P < 0.001）。ZJ-43（100 mg·kg ~（-1））有明显的镇痛作用（P < 0.05），并可被选择性Ⅱ型代谢型谷氨酸受体（mGIuR）拮抗剂所拮抗。这些数据表明，α-2激动剂仅在镇静剂量下产生镇痛作用，氯胺酮而不是MK-801，与镇痛反应有关，没有明显的副作用。ZJ-43的作用是通过激活II组mGluRs介导的。
Purpose: Not all bone cancer pain can be effectively treated with current therapies. In the present study, the effects of ip administration of alpha-2 agonists (dexmedetomidine and clonidine), N-methyl-D-aspartate (NMDA) antagonists (MK-801 and ketamine), an N-acetylaspartylglutamate peptidase inhibitor (ZJ-43), and morphine were examined in a mouse bone cancer pain model.Methods: A bone cancer pain model was produced by injection of murine sarcoma cells into the medullary cavity of the distal femur. To estimate the level of bone cancer pain, the number of pain-related behaviours induced by repeated applications of a von Frey monofilament (0.166 g) to the site of tumour cells implantation was counted. Drugs were administered two weeks after the implantation.Results: Morphine produced a significant analgesic effect (P < 0.001). The alpha-2 agonists produced analgesic effects (P < 0.001) with an efficacy similar to that of morphine, but only at doses that produced severe sedation. MK-801 had only limited analgesic effects, while ketamine produced an analgesic effect (P < 0.001) with the same efficacy as morphine. ZJ-43 (100 mg-kg(-1)) had a significant analgesic effect (P < 0.05) and the effect of ZJ-43 was antagonized by the selective group II metabotropic glutamate receptor (mGIuR) antagonist.Conclusion: These data suggest that alpha-2 agonists produce an analgesic effect only at a sedative dose and that ketamine, but not MK-801, is associated with an analgesic response without overt side effects. The effect of ZJ-43 is mediated by activating group II mGluRs.