Mayer David J, Mao Jianren, Price Donald D
Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Pain. 1995 Jun;61(3):365-374. doi: 10.1016/0304-3959(95)00023-L.
The development of tolerance to the analgesic effects of morphine as well as morphine dependence were greatly reduced by co-administration with morphine of GM1 ganglioside, a substance reported to block the translocation of protein kinase C (PKC) from cytosol to membrane of neurons. Rats made tolerant to intrathecal administration of morphine showed increased membrane-bound PKC in the superficial layers (laminae I and II) of the spinal cord dorsal horn but not in deeper layers. This increase was prevented by co-administration with morphine of GM1 ganglioside. These results indicate that the translocation and activation of PKC may be a critical step in the development of opiate tolerance and dependence. Modulation of PKC translocation and activation may prove useful for the management of pain and opiate addiction.
与吗啡共同给药的GM1神经节苷脂（一种据报道可阻止蛋白激酶C（PKC）从神经元胞质溶胶向膜转运的物质）可大大降低对吗啡镇痛作用的耐受性以及吗啡依赖性的发展。对鞘内注射吗啡产生耐受性的大鼠，脊髓背角表层（I层和II层）膜结合型PKC增加，而深层则未增加。GM1神经节苷脂与吗啡共同给药可防止这种增加。这些结果表明，PKC的转运和激活可能是阿片类药物耐受性和依赖性发展的关键步骤。调节PKC的转运和激活可能对疼痛管理和阿片类药物成瘾有用。
