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将小干扰RNA直接应用于体内疼痛研究。

Direct application of siRNA for in vivo pain research.

作者信息

Sarret Philippe, Doré-Savard Louis, Beaudet Nicolas

机构信息

Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.

出版信息

Methods Mol Biol. 2010;623:383-95. doi: 10.1007/978-1-60761-588-0_25.

DOI:10.1007/978-1-60761-588-0_25
PMID:20217565
Abstract

Pain is the new burden of the twenty-first century, raising enormous socio-economic costs to developed and underdeveloped countries. Chronic pain is a central nervous system (CNS) pathology, affecting a large proportion of the population. Morphine and its derivatives are still the golden clinical standards for treating pain although they induce severe side effects. To this day, we still have poor understanding of nociceptive pain and its underlying complex mechanisms; furthermore, novelty in clinical analgesics is lacking.RNA interference technologies are promising both for pain research and treatment. This genetic approach will likely provide new insights into pain mechanisms and eventually offer nonpharmacological therapeutic approaches. In vivo research is thus crucial to reach this goal. Preclinical studies on rodents are necessary to validate small interfering RNA (siRNA) candidates and to target precise physiological pain modulators. Aiming treatment at the CNS is delicate work, and here we will describe how to perform adequate pain research using siRNA, including siRNA preparation and injection, animal behavioral models, and CNS tissue collection.

摘要

疼痛是21世纪的新负担,给发达国家和不发达国家带来了巨大的社会经济成本。慢性疼痛是一种中枢神经系统(CNS)病理学疾病,影响着很大一部分人口。吗啡及其衍生物仍然是治疗疼痛的黄金临床标准,尽管它们会引发严重的副作用。时至今日,我们对伤害性疼痛及其潜在的复杂机制仍知之甚少;此外,临床镇痛药缺乏创新性。RNA干扰技术在疼痛研究和治疗方面都很有前景。这种基因方法可能会为疼痛机制提供新的见解,并最终提供非药物治疗方法。因此,体内研究对于实现这一目标至关重要。对啮齿动物进行临床前研究对于验证小干扰RNA(siRNA)候选物和靶向精确的生理性疼痛调节因子是必要的。针对中枢神经系统进行治疗是一项精细的工作,在此我们将描述如何使用siRNA进行充分的疼痛研究,包括siRNA的制备和注射、动物行为模型以及中枢神经系统组织采集。

相似文献

1
Direct application of siRNA for in vivo pain research.将小干扰RNA直接应用于体内疼痛研究。
Methods Mol Biol. 2010;623:383-95. doi: 10.1007/978-1-60761-588-0_25.
2
RNA interference in pain research.疼痛研究中的RNA干扰
J Neurochem. 2006 Oct;99(2):371-80. doi: 10.1111/j.1471-4159.2006.04082.x.
3
Antisense and RNA interference approaches to target validation in pain research.用于疼痛研究中靶点验证的反义核酸和RNA干扰方法。
Curr Opin Drug Discov Devel. 2004 Mar;7(2):179-87.
4
Gene silencing through RNA interference (RNAi) in vivo: strategies based on the direct application of siRNAs.体内通过RNA干扰(RNAi)实现基因沉默:基于直接应用小干扰RNA(siRNA)的策略。
J Biotechnol. 2006 Jun 25;124(1):12-25. doi: 10.1016/j.jbiotec.2005.12.003. Epub 2006 Jan 18.
5
In vivo pharmacokinetics, tissue distribution and underlying mechanisms of various PEI(-PEG)/siRNA complexes.各种聚乙烯亚胺(-聚乙二醇)/小干扰RNA复合物的体内药代动力学、组织分布及潜在机制
Toxicol Appl Pharmacol. 2009 Apr 1;236(1):97-108. doi: 10.1016/j.taap.2009.01.014. Epub 2009 Jan 29.
6
Rational design and in vitro and in vivo delivery of Dicer substrate siRNA.Dicer底物小干扰RNA的合理设计及其体内外递送
Nat Protoc. 2006;1(2):508-17. doi: 10.1038/nprot.2006.72.
7
siRNA relieves chronic neuropathic pain.小干扰RNA可缓解慢性神经性疼痛。
Nucleic Acids Res. 2004 Mar 16;32(5):e49. doi: 10.1093/nar/gnh044.
8
Effects of treatment with small interfering RNA on joint inflammation in mice with collagen-induced arthritis.小干扰RNA治疗对胶原诱导性关节炎小鼠关节炎症的影响。
Arthritis Rheum. 2005 Apr;52(4):1314-8. doi: 10.1002/art.20975.
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Hydrodynamic delivery protocols.流体动力学给药方案。
Methods Mol Biol. 2010;623:189-95. doi: 10.1007/978-1-60761-588-0_12.
10
[Development of antituberculous drugs: current status and future prospects].[抗结核药物的研发:现状与未来前景]
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