Expression of opioid receptors and c-fos in CB1 knockout mice exposed to neuropathic pain

Expression of opioid receptors and c-fos in CB1 knockout mice exposed to neuropathic pain
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DOI:
10.1016/j.neuropharm.2005.11.002
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发表时间:
2006-01-01
期刊:
影响因子:
4.7
通讯作者:
Maldonado, R
Maldonado, R
中科院分区:
医学2区
文献类型:
--
作者:
Pol, O;Murtra, P;Maldonado, R

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神经性疼痛的发生与发生在背根神经节(DRG)和脊髓的多种基因表达变化有关。本研究的目的是评估CB1大麻素受体基因的破坏是否调节神经性疼痛引起的DRG和脊髓中mu- (MOR), delta- (DOR)和kappa-阿片受体(KOR) mRNA表达水平的变化。在这些动物中还评估了c-fos在脊髓腰椎和骶区表达的诱导作用。real-time PCR检测阿片受体mRNA水平,免疫组织化学检测Fos蛋白水平。神经损伤显著降低CB1大麻素敲除(KO)小鼠和野生型窝鼠(WT) DRG和脊髓腰椎段MOR的表达。相比之下,DOR和KOR的mRNA水平在分析的任何不同切片中都没有显著变化。此外,坐骨神经损伤引起KO和WT的腰椎和骶区脊髓c-fos表达相似的增加。在所有情况下,WT和KO小鼠之间没有观察到显著差异。这些数据揭示了神经性疼痛引起的DRG和/或脊髓中MOR表达和c-fos水平的特异性变化,这些变化不受CB1大麻素受体遗传破坏的影响。(c) 2005 Elsevier Ltd版权所有。
The development of neuropathic pain is associated with multiple changes in gene expression occurring in the dorsal root ganglia (DRG) and spinal cord. The goal of this study was to evaluate whether the disruption of CB1 cannabinoid receptor gene modulates the changes induced by neuropathic pain in the expression of mu- (MOR), delta- (DOR) and kappa-opioid receptors (KOR) mRNA levels in the DRG and spinal cord. The induction of c-fos expression in the lumbar and sacral regions of the spinal cord was also evaluated in these animals. Opioid receptors mRNA levels were determined by using real-time PCR and Fos protein levels by immunohistochemistry. Nerve injury significantly reduced the expression of MOR in the DRG and the lumbar section of the spinal cord from CB1 cannabinoid knockout (KO) mice and wild-type littermates (WT). In contrast, mRNA levels of DOR and KOR were not significantly changed in any of the different sections analysed. Furthermore, sciatic nerve injury evoked a similar increase of c-fos expression in lumbar and sacral regions of the spinal cord of both KO and WT. In all instances, no significant differences were observed between WT and KO mice. These data revealed specific changes induced by neuropathic pain in MOR expression and c-fos levels in the DRG and/or spinal cord that were not modified by the genetic disruption of CB1 cannabinoid receptors. (c) 2005 Elsevier Ltd. All rights reserved.