μ-Opioid Receptor Antibody Reveals Tissue-Dependent Specific Staining and Increased Neuronal μ-Receptor Immunoreactivity at the Injured Nerve Trunk in Mice
μ-Opioid Receptor Antibody Reveals Tissue-Dependent Specific Staining and Increased Neuronal μ-Receptor Immunoreactivity at the Injured Nerve Trunk in Mice
复制标题
μ-阿片受体抗体显示小鼠受损神经干处的组织依赖性特异性染色和神经元 μ-受体免疫反应性增加
作者：
Y. Schmidt;C. Gaveriaux;H. Machelska
神经性疼痛是一种使人衰弱的慢性疾病，通常由周围神经损伤引起。激活外周感觉神经元上的阿片受体可以减轻疼痛，而不会产生中枢神经系统副作用。在这里，我们的目的是分析神经元μ阿片受体（控制临床疼痛最相关的阿片受体）沿着神经病变的周围神经元通路的分布。因此，在小鼠坐骨神经慢性收缩损伤后，我们使用免疫组织化学来量化背根神经节（DRG）、直接位于受伤神经干及其后爪皮肤外周末梢的μ受体蛋白表达。我们还彻底检查了 μ 受体抗体染色特异性。我们发现，该抗体特异性标记人胚胎肾 293 细胞以及坐骨神经和后爪皮肤真皮的神经元突中的 μ 受体，但令人惊讶的是，根据使用 μ/δ/κ-阿片受体敲除小鼠的判断，DRG 中却没有。因此，不可能对 DRG 中的 μ 受体表达进行可靠的定量分析。然而，我们证明，在受伤后第 2 天和第 14 天，神经干损伤附近的 μ 受体免疫反应性强烈增强，但爪子中的免疫反应性没有改变。因此，轴突损伤部位的μ-阿片受体可能是控制疼痛性神经病的一个有希望的靶点。此外，我们的研究结果表明抗体特异性具有严格的组织依赖性特征，最好使用基因敲除动物。
Neuropathic pain is a debilitating chronic disease often resulting from damage to peripheral nerves. Activation of opioid receptors on peripheral sensory neurons can attenuate pain without central nervous system side effects. Here we aimed to analyze the distribution of neuronal μ-opioid receptors, the most relevant opioid receptors in the control of clinical pain, along the peripheral neuronal pathways in neuropathy. Hence, following a chronic constriction injury of the sciatic nerve in mice, we used immunohistochemistry to quantify the μ-receptor protein expression in the dorsal root ganglia (DRG), directly at the injured nerve trunk, and at its peripheral endings in the hind paw skin. We also thoroughly examined the μ-receptor antibody staining specificity. We found that the antibody specifically labeled μ-receptors in human embryonic kidney 293 cells as well as in neuronal processes of the sciatic nerve and hind paw skin dermis, but surprisingly not in the DRG, as judged by the use of μ/δ/κ-opioid receptor knockout mice. Therefore, a reliable quantitative analysis of μ-receptor expression in the DRG was not possible. However, we demonstrate that the μ-receptor immunoreactivity was strongly enhanced proximally to the injury at the nerve trunk, but was unaltered in paws, on days 2 and 14 following injury. Thus, μ-opioid receptors at the site of axonal damage might be a promising target for the control of painful neuropathies. Furthermore, our findings suggest a rigorous tissue-dependent characterization of antibodies' specificity, preferably using knockout animals.
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影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
DOI：
10.1016/j.ejpain.2010.11.018
发表时间：
2011-08
期刊：
European journal of pain (London, England)
影响因子：
--
作者：
Lee CY;Perez FM;Wang W;Guan X;Zhao X;Fisher JL;Guan Y;Sweitzer SM;Raja SN;Tao YX
通讯作者：
Tao YX
DOI：
10.1073/pnas.0603359103
发表时间：
2006-06-20
影响因子：
11.1
作者：
Scherrer, Gregory;Tryoen-Toth, Petra;Kieffer, Brigitte L.
通讯作者：
Kieffer, Brigitte L.
RNA 高速公路：用于轴突生长的 kappa 阿片受体 mRNA 的轴突 RNA 运输。
DOI：
10.1039/c0ib00107d
发表时间：
2011
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Wei,Li-Na
通讯作者：
Wei,Li-Na