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镇痛研究中的离子通道

Ion channels in analgesia research.

作者信息

Rosenbaum Tamara, Simon Sidney A, Islas Leon D

机构信息

Departamento de Biofísica, Instituto de Fisiología Celular, Ciudad Universitaria, Universidad Nacional Autonóma de México, Mexico City, Mexico.

出版信息

Methods Mol Biol. 2010;617:223-36. doi: 10.1007/978-1-60327-323-7_18.

DOI:10.1007/978-1-60327-323-7_18
PMID:20336426
Abstract

Several recent techniques have allowed us to pinpoint the receptors responsible for the detection of nociceptive stimuli. Among these receptors, ion channels play a fundamental role in the recognition and transduction of stimuli that can cause pain. During the last decade, compelling evidence has been gathered on the role of the TRPV1 channel in inflammatory and neuropathic states. Activation of TRPV1 in nociceptive neurons results in the release of neuropeptides and transmitters, leading to the generation of action potentials that will be sent to higher CNS areas, where they will often be perceived as pain. Its activation will also evoke the peripheral release of pro-inflammatory compounds that may sensitize other neurons to physical, thermal, or chemical stimuli. For these reasons, and because its continuous activation causes analgesia, TRPV1 is now considered a viable drug target for clinical use in the management of pain. Using the TRPV1 channel as an example, here we describe some basic biophysical approaches used to study the properties of ion channels involved in pain and in analgesia.

摘要

最近的几项技术使我们能够确定负责检测伤害性刺激的受体。在这些受体中,离子通道在识别和转导可导致疼痛的刺激方面发挥着重要作用。在过去十年中,关于TRPV1通道在炎症和神经病理性状态中的作用已经收集了令人信服的证据。伤害性神经元中TRPV1的激活导致神经肽和递质的释放,从而产生动作电位,这些动作电位将被发送到更高的中枢神经系统区域,在那里它们通常会被感知为疼痛。其激活还将引发促炎化合物的外周释放,这些化合物可能会使其他神经元对物理、热或化学刺激敏感。由于这些原因,并且因为其持续激活会导致镇痛作用,TRPV1现在被认为是疼痛管理临床应用中可行的药物靶点。以TRPV1通道为例,我们在此描述一些用于研究参与疼痛和镇痛的离子通道特性的基本生物物理方法。

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1
Ion channels in analgesia research.镇痛研究中的离子通道
Methods Mol Biol. 2010;617:223-36. doi: 10.1007/978-1-60327-323-7_18.
2
[The TRPV1 channel as a target for the treatment of pain].[作为疼痛治疗靶点的瞬时受体电位香草酸亚型1(TRPV1)通道]
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Brain Res Rev. 2009 Apr;60(1):267-77. doi: 10.1016/j.brainresrev.2008.12.006. Epub 2008 Dec 25.
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The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats and mice.辣椒素受体TRPV1和酸敏感离子通道(ASICs)在大鼠和小鼠初级伤害性神经元亚群质子敏感性中的作用。
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Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers.通过TRPV1介导的非渗透性钠通道阻滞剂的进入来抑制伤害感受器。
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TRPV1b overexpression negatively regulates TRPV1 responsiveness to capsaicin, heat and low pH in HEK293 cells.TRPV1b的过表达对人胚肾细胞293(HEK293细胞)中TRPV1对辣椒素、热和低pH的反应性起负调控作用。
J Neurochem. 2006 Nov;99(4):1088-102. doi: 10.1111/j.1471-4159.2006.04145.x.

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Biophys J. 2013 May 21;104(10):2160-9. doi: 10.1016/j.bpj.2013.03.055.