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本文引用的文献

1
dextro- and levo-morphine attenuate opioid delta and kappa receptor agonist produced analgesia in mu-opioid receptor knockout mice.右旋吗啡和左旋吗啡可减弱阿片δ和κ受体激动剂在μ阿片受体基因敲除小鼠中产生的镇痛作用。
Eur J Pharmacol. 2006 Feb 15;531(1-3):103-7. doi: 10.1016/j.ejphar.2005.12.012. Epub 2006 Jan 30.
2
Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance.脊髓小胶质细胞中p38丝裂原活化蛋白激酶的激活介导吗啡镇痛耐受性。
Brain Res. 2006 Jan 19;1069(1):235-43. doi: 10.1016/j.brainres.2005.11.066. Epub 2006 Jan 3.
3
Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis.p38丝裂原活化蛋白激酶对EEA1的磷酸化作用调节μ阿片受体的内吞作用。
EMBO J. 2005 Sep 21;24(18):3235-46. doi: 10.1038/sj.emboj.7600799. Epub 2005 Sep 1.
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Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.抗镇痛作用：右吗啡对左吗啡在小鼠脊髓胶质细胞上的立体选择性作用。
J Pharmacol Exp Ther. 2005 Sep;314(3):1101-8. doi: 10.1124/jpet.105.087130. Epub 2005 May 18.
5
Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization.脊髓p38β亚型介导组织损伤诱导的痛觉过敏和脊髓敏化。
J Neurochem. 2005 Mar;92(6):1508-20. doi: 10.1111/j.1471-4159.2004.02996.x.
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Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord.介导吗啡诱导小鼠脊髓抗镇痛作用的非阿片能机制。
J Pharmacol Exp Ther. 2004 Jul;310(1):240-6. doi: 10.1124/jpet.104.065334. Epub 2004 Mar 3.
7
Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury.脊髓中过度活跃的小胶质细胞中p38丝裂原活化蛋白激酶的激活会导致周围神经损伤后的疼痛超敏反应。
Glia. 2004 Jan 1;45(1):89-95. doi: 10.1002/glia.10308.
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p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases.p38丝裂原活化蛋白激酶：作为炎症性疾病治疗靶点的关键信号分子
Nat Rev Drug Discov. 2003 Sep;2(9):717-26. doi: 10.1038/nrd1177.
9
Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing.脊髓小胶质细胞中p38丝裂原活化蛋白激酶的激活是炎症诱导的脊髓疼痛处理中的关键环节。
J Neurochem. 2003 Sep;86(6):1534-44. doi: 10.1046/j.1471-4159.2003.01969.x.
10
p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain.p38丝裂原活化蛋白激酶在脊髓小胶质细胞和背根神经节神经元的脊髓神经结扎后被激活，并有助于神经性疼痛的产生。
J Neurosci. 2003 May 15;23(10):4017-22. doi: 10.1523/JNEUROSCI.23-10-04017.2003.

p38丝裂原活化蛋白激酶抑制剂SB203580可逆转右美沙芬或吗啡在小鼠脊髓中诱导的抗镇痛作用。

p38 mitogen-activated protein kinase inhibitor SB203580 reverses the antianalgesia induced by dextro-morphine or morphine in the mouse spinal cord.

作者信息

Wu Hsiang-En, Sun Han-Sen, Cheng Caleb W, Tseng Leon F

机构信息

Department of Anesthesiology, Medical College of Wisconsin, Medical Education Building, Room M4308, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

出版信息

Eur J Pharmacol. 2006 Nov 21;550(1-3):91-4. doi: 10.1016/j.ejphar.2006.08.060. Epub 2006 Sep 8.

DOI:10.1016/j.ejphar.2006.08.060
PMID:17026985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1850335/
Abstract

We have previously demonstrated that intrathecal pretreatment with dextro-morphine or morphine attenuates the morphine-produced antinociception. The phenomenon has been defined as antianalgesia, which is mediated by a non-opioid receptor [Wu, H., Thompson, J., Sun, H., Terashvili, M., Tseng, L.F., 2005. Antianalgesia: stereo-selective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord. J. Pharmacol. Exp. Ther. 314, 1101-1108]. To determine if p38 mitogen-activated protein kinase (MAPK) is involved in the antianalgesia, the effects of p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) on the attenuation of the morphine-produced tail-flick inhibition induced by dextro-morphine or morphine were studied in male CD-1 mice. Intrathecal pretreatment with SB203580 (24.2 nmol) reversed the attenuation of the morphine-produced tail-flick inhibition induced by dextro-morphine (33 fmol) or morphine (0.3 nmol) pretreatment. The finding indicates that the antianalgesia induced by dextro-morphine or morphine is mediated by the activation of p38 MAPK in the mouse spinal cord.

摘要

我们之前已经证明，鞘内注射右美沙芬或吗啡预处理可减弱吗啡产生的镇痛作用。这种现象被定义为抗镇痛，它是由一种非阿片受体介导的[Wu, H., Thompson, J., Sun, H., Terashvili, M., Tseng, L.F., 2005. 抗镇痛：右美沙芬对左美沙芬在小鼠脊髓胶质细胞上的立体选择性作用。《药理学与实验治疗学杂志》314, 1101 - 1108]。为了确定p38丝裂原活化蛋白激酶（MAPK）是否参与抗镇痛作用，研究了p38 MAPK抑制剂4-(4-氟苯基)-2-(4-甲亚磺酰基苯基)-5-(4-吡啶基)-1H-咪唑（SB203580）对右美沙芬或吗啡诱导的吗啡产生的甩尾抑制减弱的影响，实验采用雄性CD-1小鼠。鞘内注射SB203580（24.2 nmol）预处理可逆转右美沙芬（33 fmol）或吗啡（0.3 nmol）预处理诱导的吗啡产生的甩尾抑制减弱。这一发现表明，右美沙芬或吗啡诱导的抗镇痛作用是由小鼠脊髓中p38 MAPK的激活介导的。