Nociception and TRP Channels
Nociception and TRP Channels
复制标题
DOI：
10.2174/1568007043336789
复制
发表时间：
2004-01-01
影响因子：
3
通讯作者：
Tominaga, Makoto
中科院分区：
文献类型：
--
作者：
Numazaki, Mitsuko;Tominaga, Makoto
有害的热、机械或化学刺激通过兴奋称为伤害性感受器的外周末梢引起疼痛，多种离子型和代谢型受体参与了这一过程。辣椒素受体TRPV 1是辣椒素作用的分子靶点，是一种伤害感受器特异性离子通道。TRPV 1不仅可以被辣椒素激活，还可以被有害的热（热阈值>43摄氏度）或质子（酸化）激活，所有这些都是已知的体内疼痛。使用TRPV 1缺陷小鼠的研究表明，TRPV 1对于疼痛感觉的选择性方式和热痛觉过敏是必不可少的。由组织损伤/炎症引发并以超敏反应为特征的炎性疼痛的一种潜在机制是TRPV 1的致敏作用。除TRPV 1外，哺乳动物中还有5种热敏离子通道，均属于TRP（瞬时受体电位）超家族。其中包括TRPV 2、TRPV 3、TRPV 4、TRPM 8和TRPA 1。这些通道表现出不同的热激活阈值（TRPV 2> 52摄氏度，TRPV 3>类似于34-38摄氏度，TRPV 4>类似于27-35摄氏度，TRPM 8 <类似于25-28摄氏度，TRPA 1 < 17摄氏度），并在初级感觉神经元以及其他组织中表达。一些热敏TRP通道可能参与热伤害感受，因为它们的激活阈值在有害温度范围内。
Noxious thermal, mechanical, or chemical stimuli evoke pain through excitation of the peripheral terminals called nociceptor, and many kinds of ionotropic and metabotropic receptors are involved in this process. Capsaicin receptor TRPV1 is a nociceptor-spesific ion channel that serves as the molecular target of capsaicin. TRPV1 can be activated not only by capsaicin but also by noxious heat (with a thermal threshold >43 degrees C) or protons (acidification), all of which are known to cause pain in vivo. Studies using TRPV1-deficient mice have shown that TRPV1 is essential for selective modalities of pain sensation and for thermal hyperalgesia. One mechanism underlying inflammatory pain which is initiated by tissue damage/inflammation and characterized by hypersensitivity is sensitization of TRPV1. In addition to TRPV1, there are five thermosensitive ion channels in mammals, all of which belong to the TRP (transient receptor potential) super family. These include TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1. These channels exhibit distinct thermal activation thresholds (> 52 degrees C for TRPV2, > similar to 34-38 degrees C for TRPV3, > similar to 27-35 degrees C for TRPV4, < similar to 25-28 degrees C for TRPM8 and < 17 degrees C for TRPA1) and are expressed in primary sensory neurons as well as other tissues. Some of the thermosensitive TRP channels are likely to be involved in thermal nociception, since their activation thresholds are within the noxious range of temperatures.