Coexpression of vanilloid receptor subtype-1 and acid-sensing ion channel genes in the human trigeminal ganglion neurons
Coexpression of vanilloid receptor subtype-1 and acid-sensing ion channel genes in the human trigeminal ganglion neurons
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DOI：
10.1093/chemse/bjh181
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Shimada, S
中科院分区：
文献类型：
--
作者：
Ugawa, S;Ueda, T;Shimada, S
先前的心理物理学实验已经表明，在人舌头的背表面的一侧重复施加高浓度的酸引起刺激或疼痛（Dessirier等人，2000）。在酸化下，从酸解离的质子可能激活源自三叉神经节的局部伤害感受器中表达的兴奋性阳离子通道，导致产生这种感觉。最近对感觉神经元的分子研究已经揭示，瞬时受体电位/香草素受体亚型-1（TRPV 1）和酸敏感离子通道（ASIC）介导哺乳动物中质子诱导的刺激或伤害感受的大部分（Julius和Basbaum，2001; Ugawa等人，2003年）。在这里，我们提供的证据参与这两个渠道在人类酸诱发疼痛，并显示其相对贡献酸诱发的伤害性感受。在我们的人类疼痛模型（由名古屋城市大学伦理委员会批准，并根据赫尔辛基宣言进行）中，将酸性溶液（pH≥ 6.0）直接输注到人类皮肤中引起局部疼痛，这种疼痛可被阿米洛利（一种ASIC抑制剂）阻断，但不能被辣椒平（一种TRPV 1抑制剂）阻断。虽然阿米洛利的疗效只有部分衰减下更严重的酸化（pH 5.0），辣椒平产生一些阻断作用pH 5诱发的疼痛。
Previous psychophysical experiments have shown that repeated applications of high concentrations of acids on one side of the dorsal surface of the human tongue evoke irritation or pain (Dessirier et al., 2000). Under acidification, protons dissociated from the acids probably activate excitatory cation channels expressed in local nociceptors that originate from trigeminal ganglia, leading to the generation of such sensations. Recent molecular investigations into sensory neurons have revealed that a transient receptor potential/vanilloid receptor subtype-1 (TRPV1) and an acid-sensing ion channel (ASIC) mediate the greater part of proton-induced irritation or nociception in mammals (Julius and Basbaum, 2001; Ugawa et al., 2003). Here we provide evidence for involvement of both channels in acid-evoked pain in humans and show their relative contributions to acid-evoked nociception. In our human pain model (approved by the Ethics Committee of Nagoya City University and conducted in accordance with the Declaration of Helsinki), direct infusion of acidic solutions (pH≥ 6.0) into human skin caused localized pain, which was blocked by amiloride, an inhibitor of ASICs, but not by capsazepine, an inhibitor of TRPV1. Although the efficacy of amiloride was only partially attenuated under more severe acidification (pH 5.0), capsazepine produced some blocking effect on pH 5-evoked pain.