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帕罗西汀对神经病理性疼痛的影响:一项分子研究。

Effect of Paroxetine on the Neuropathic Pain: A Molecular Study.

机构信息

Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran Biomed J. 2020 Sep;24(5):306-13. doi: 10.29252/ibj.24.5.301. Epub 2020 May 2.

DOI:10.29252/ibj.24.5.301
PMID:32429644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7392138/
Abstract

BACKGROUND

Neuropathic pain, due to peripheral nerve damage, has influenced millions of people living all over the world. It has been shown that paroxetine can relieve neuropathic pain. Recently, the role of certain proteins like brain-derived neurotrophic factor (BDNF), GABAA receptor, and K+-Cl- cotransporter 2 (KCC2) transporter in the occurrence of neuropathic pain has been documented. In the current study, the expression of these proteins affected by paroxetine was evaluated.

METHODS

Male Wistar rats were allocated into two main groups of pre- and post-injury. Rats in each main group received paroxetine before nerve injury and at day seven after nerve damage till day 14, respectively. The lumbar spinal cord of animals was extracted to assess the expression of target genes and proteins.

RESULTS

In the preventive study, paroxetine decreased BDNF and increased KCC2 and GABAA gene and protein expression, while in the post-injury paradigm, it decreased BDNF and increased KCC2 genes and protein expression. In this regard, an increase in the protein expression of GABAA was observed.

CONCLUSION

It seems that paroxetine with a change in the expression of three significant proteins involved in neuropathic pain could attenuate this type of chronic pain.

摘要

背景

外周神经损伤引起的神经性疼痛影响了全球数百万人的生活。已有研究表明,帕罗西汀可以缓解神经性疼痛。最近,某些蛋白质(如脑源性神经营养因子(BDNF)、GABAA 受体和 K+-Cl-共转运蛋白 2(KCC2)转运体)在神经性疼痛发生中的作用已被记录在案。在本研究中,评估了帕罗西汀对这些蛋白质表达的影响。

方法

雄性 Wistar 大鼠被分为损伤前和损伤后两个主要组。每组大鼠分别在神经损伤前和损伤后第 7 天至第 14 天给予帕罗西汀。提取动物的腰椎脊髓以评估靶基因和蛋白质的表达。

结果

在预防研究中,帕罗西汀降低了 BDNF 并增加了 KCC2 和 GABAA 基因和蛋白质的表达,而在损伤后模型中,它降低了 BDNF 并增加了 KCC2 基因和蛋白质的表达。在这方面,观察到 GABAA 蛋白表达增加。

结论

帕罗西汀似乎通过改变三种与神经性疼痛相关的重要蛋白质的表达来减轻这种慢性疼痛。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/51b388011340/ibj-24-306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/38be1f4c9d34/ibj-24-306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/b480f6f79c1a/ibj-24-306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/3b1c42b583e7/ibj-24-306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/51b388011340/ibj-24-306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/38be1f4c9d34/ibj-24-306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/b480f6f79c1a/ibj-24-306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/3b1c42b583e7/ibj-24-306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30a2/7392138/51b388011340/ibj-24-306-g004.jpg

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本文引用的文献

1
Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain.帕罗西汀可减轻神经病理性疼痛大鼠模型中的疼痛发展及现有疼痛。
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P2X4 purinoceptor signaling in chronic pain.P2X4 嘌呤能受体信号在慢性疼痛中的作用。
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Purinergic systems, neuropathic pain and the role of microglia.嘌呤能系统、神经病理性疼痛和小胶质细胞的作用。
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Exp Neurol. 2010 Apr;222(2):256-66. doi: 10.1016/j.expneurol.2010.01.003. Epub 2010 Jan 14.
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P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation.小胶质细胞中P2X4受体介导的脑源性神经营养因子的合成与释放依赖于钙和p38丝裂原活化蛋白激酶的激活。
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