Dynamic temporal and spatial regulation of mu opioid receptor expression in primary afferent neurons following spinal nerve injury.
Dynamic temporal and spatial regulation of mu opioid receptor expression in primary afferent neurons following spinal nerve injury.
复制标题
DOI：
10.1016/j.ejpain.2010.11.018
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Lee CY;Perez FM;Wang W;Guan X;Zhao X;Fisher JL;Guan Y;Sweitzer SM;Raja SN;Tao YX
尽管使用处方止痛药，患有神经性疼痛的患者仍然会经历中度到重度疼痛。越来越多的人认识到，在炎性和神经性疼痛模型中，外周阿片类药物具有强效镇痛作用。本研究的目的是表征大鼠L5脊髓神经结扎模型中原发性传入神经元中mu阿片受体（mOR） mRNA和蛋白的时空表达。于脊髓神经结扎或假手术后第0、3、7、14、35天采集双侧L4、L5背根神经节（DRGs）、L4、L5脊髓节段和后爪足底皮肤（naïve）。我们发现，L5脊髓神经结扎后，初级传入神经元中mOR mRNA和蛋白的表达发生了动态和部位特异性的变化。Real-time RT-PCR、免疫组织化学和Western blot分析显示L5 DRG中mOR mRNA和蛋白表达下调。相比之下，在未损伤的L4 DRG中，mOR mRNA在第7天短暂下降，然后在第14天显著增加。Western blot分析显示mOR蛋白表达持续增加，尽管免疫组化显示未损伤L4 DRG中mOR阳性神经元数量没有变化。有趣的是，在神经损伤后第14天和第35天，皮肤和L4和L5脊髓中更多的or蛋白表达减少。神经损伤后mOR表达的这些时间和解剖特异性变化可能对疼痛相关行为和阿片类镇痛产生功能影响。
Despite using prescribed pain medications, patients with neuropathic pain continue to experience moderate to severe pain. There is a growing recognition of a potent peripheral opioid analgesia in models of inflammatory and neuropathic pain. The goal of this study was to characterize the temporal and spatial expression of mu opioid receptor (mOR) mRNA and protein in primary afferent neurons in a rat L5 spinal nerve ligation model of persistent neuropathic pain. Bilateral L4 and L5 dorsal root ganglia (DRGs), L4 and L5 spinal cord segments, and hind paw plantar skins were collected on days 0 (naïve), 3, 7, 14, and 35 post-spinal nerve ligation or post-sham surgery. We found that expression of mOR mRNA and protein in primary afferent neurons changed dynamically and site-specifically following L5 spinal nerve ligation. Real-time RT-PCR, immunohistochemistry, and Western blot analysis demonstrated a down-regulation of mOR mRNA and protein in the injured L5 DRG. In contrast, in the uninjured L4 DRG, mOR mRNA transiently decreased on day 7 and then increased significantly on day 14. Western blot analysis revealed a persistent increase in mOR protein expression, although immunohistochemistry showed no change in number of mOR-positive neurons in the uninjured L4 DRG. Interestingly, mOR protein expression was reduced in the skin on days 14 and 35 post-nerve injury and in the L4 and L5 spinal cord on day 35 post-nerve injury. These temporal and anatomically specific changes in mOR expression following nerve injury are likely to have functional consequences on pain-associated behaviors and opioid analgesia.
登录
查看更多内容
周围神经损伤后脊髓背角突触体相关蛋白的蛋白质组。
影响因子：
3.4
作者：
Singh, Om V.;Yaster, Myron;Xu, Ji-Tian;Guan, Yun;Guan, Xiaowei;Dharmarajan, Arun M.;Raja, Srinivasa N.;Zeitlin, Pamela L.;Tao, Yuan-Xiang
通讯作者：
Tao, Yuan-Xiang
影响因子：
6.1
作者：
Lewanowitsch, T;Miller, JH;Irvine, RJ
通讯作者：
Irvine, RJ
影响因子：
5
作者：
Obara, Ilona;Makuch, Wioletta;Przewlocka, Barbara
通讯作者：
Przewlocka, Barbara
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
7.4
作者：
Obara, Ilona;Parkitna, Jan Rodriguez;Przewlocki, Ryszard
通讯作者：
Przewlocki, Ryszard