Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors
Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors
复制标题
DOI：
10.1073/pnas.93.3.1108
复制
发表时间：
1996-02-06
影响因子：
11.1
通讯作者：
Levine, JD
中科院分区：
文献类型：
--
作者：
Gold, MS;Reichling, DB;Levine, JD
初级传入神经元的敏化是与组织损伤和炎症相关的疼痛和压痛的基础，兴奋性的增加是由损伤部位释放的化学物质引起的。由于最近的研究表明，电压门控性钠电流的增加可能是与损伤相关的神经元兴奋性增加的基础。我们检验了一种假说，即在具有伤害性感受器特性的感觉神经元亚群中选择性表达的河豚毒素抗性电压门控性钠电流(TTX-RI-Na)是痛敏药物的靶点。我们的结果表明，在体内产生压痛或痛觉过敏的三种药物：前列腺素E(2)、腺苷和血清素调节河豚毒素受体I-Na。这些药物增加了电流的大小，使其电导-电压关系向超极化方向移动，增加了其激活和失活的速度，而不产生痛觉过敏的环氧合酶产物血栓素B-2对TTX-RI-Na没有影响。这些结果表明，TTX-Ri-Na的调节是哺乳动物伤害性感受器敏化的机制之一。
Sensitization of primary afferent neurons underlies much of the pain and tenderness associated with tissue injury and inflammation, The increase in excitability is caused by chemical agents released at the site of injury, Because recent studies suggest that an increase in voltage-gated Na+ currents may underlie increases in neuronal excitability associated with injury, we have tested the hypothesis that a tetrodotoxin-resistant voltage-gated Na+ current (TTX-R I-Na), selectively expressed in a subpopulation of sensory neurons with properties of nociceptors, is a target for hyperalgesic agents, Our results indicate that three agents that produce tenderness or hyperalgesia in vivo, prostaglandin E(2), adenosine, and serotonin, modulate TTX-R I-Na. These agents increase the magnitude of the current, shift its conductance-voltage relationship in a hyperpolarized direction, and increase its rate of activation and inactivation, In contrast, thromboxane B-2, a cyclooxygenase product that does not produce hyperalgesia, did not affect TTX-R I-Na. These results suggest that modulation of TTX-R I-Na is a mechanism for sensitization of mammalian nociceptors.