Alternation of Signal Transduction and Desensitization by Repeated Morphine Treatment in the Presense of Chronic Oain.

在慢性疼痛的情况下通过重复吗啡治疗来改变信号转导和脱敏。

• 批准号: 14572163
• 负责人: TOKUYAMA Shogo
• 金额: $ 1.92万
• 依托单位: Kobe Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572163/
• 关键词: chronic pain; pain stimulation; morphine; tolerance; neuronal cell adhesion molecule; NCAM; PKC; 細胞内情報伝達; κオピオイド受容体; μオピオイド受容体

It has been reported that induction of m-opioid receptors is affected by neuronal cell adhesion molecule (NCAM) in the experiment used by P19 cell line, suggesting that morphine action might be modulated by NCAM. In the present study, involvement of NCAM in the development of tolerance to morphine analgesia was examined. The tolerance was easily developed by daily injection of 10 mg/kg morphine on mice for 5 days, as evaluated by tail-flick method. On the other hand, treatment of antisense oligodeoxynucleotides (AS-ODN) for NCAM significantly inhibited its tolerance development. Recently, desensitization of opioid receptor phosphorylated by protein kinase C (PKC) as one of the mechanisms of tolerance development has been focused. In fact, phosphorylation and expression of PKCα, one of the PKC isozymes, protein was increased in the midbrain region of morphine tolerant mice in the Western blot analysis. Furthermore, the change in PKCα protein caused by multiple treatment of morphine was also reversed by AS-ODN for NCAM. These results obtained in this study demonstrate that NCAM plays an important role in the development of tolerance to morphine mediated through the regulation of phosphorylation and expression of PKCα protein.

在P19所使用的经验中，神经元细胞粘附分子（NCAM）的影响，这表明吗啡作用可能是由NCAM调节的每天在小鼠上每天注射10 mg/kg吗啡，这是通过尾部轻巧方法评估的耐受性发展的机制实际上是PKCα的磷酸化和表达，这是PKC同工酶之一，在蛋白质印迹分析中，蛋白质在吗啡耐受性小鼠中增加了蛋白质。在这项研究中获得的这些结果表明，NCAM在耐受性的发展中起着重要的作用，介导了PKCα蛋白的磷酸化和表达的调节。