Tetrodotoxin-resistant Na+ currents and inflammatory hyperalgesia
Tetrodotoxin-resistant Na+ currents and inflammatory hyperalgesia
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DOI：
10.1073/pnas.96.14.7645
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Gold, MS
中科院分区：
文献类型：
--
作者：
Gold, MS
已经确定了几种机制可能是炎症诱导的高阈值初级传入神经元敏化的基础，包括电压和Ca 2+依赖性离子通道和负责产生发生器电位的离子通道的调制。一个这样的机制，最近已经收到了很多关注是河豚毒素（TTX）的抗电压门控Na+电流的调制。支持TTX-耐Na+电流的初级传入神经元和炎性痛觉过敏的敏化作用的证据进行了审查。这些证据来自对TTX抗性Na+电流在初级传入神经元和身体其他组织中的分布的研究，这些研究表明这些电流仅在可能参与伤害感受的初级传入神经元亚群中表达。这些电流的生物物理特性的研究数据表明，它们非常适合调解与长期膜去极化相关的重复放电。有关炎症介质和抗伤害性药物对TTX抗性Na+电流影响的研究数据表明，这些电流的调制是初级传入神经元敏化的潜在机制。此外，炎症介质诱导的这些电流调制的第二信使途径似乎是炎症介质诱导的痛觉过敏的基础。最后，最近的反义研究也产生了数据支持的作用TTX耐Na+电流在炎症性痛觉过敏。虽然这些研究的数据是令人信服的，在疼痛的神经生物学座谈会上提出的数据提出了一些有趣的问题，TTX-耐Na+电流在炎症性痛觉过敏的作用，这些问题的影响进行了讨论。
Several mechanisms have been identified that may underlie inflammation-induced sensitization of high-threshold primary afferent neurons, including the modulation of voltage- and Ca2+-dependent ion channels and ion channels responsible for the production of generator potentials. One such mechanism that has recently received a lot of attention is the modulation of a tetrodotoxin (TTX)-resistant voltage-gated Na+ current. Evidence supporting a role for TTX-resistant Na+ currents in the sensitization of primary afferent neurons and inflammatory hyperalgesia is reviewed. Such evidence is derived from studies on the distribution of TTX-resistant Na+ currents among primary afferent neurons and other tissues of the body that suggest that these currents are expressed only in a subpopulation of primary afferent neurons that are likely to be involved in nociception. Data from studies on the biophysical properties of these currents suggest that they are ideally suited to mediate the repetitive discharge associated with prolonged membrane depolarizations. Data from studies on the effects of inflammatory mediators and antinociceptive agents on TTX-resistant Na+ currents suggest that modulation of these currents is an underlying mechanism of primary afferent neuron sensitization, In addition, the second-messenger pathways underlying inflammatory mediator-induced modulation of these currents appear to underlie inflammatory mediator induced hyperalgesia. Finally, recent antisense studies have also yielded data supporting a role for TTX-resistant Na+ currents in inflammatory hyperalgesia. Although data from these studies are compelling, data presented at the Neurobiology of Pain colloquium raised a number of interesting questions regarding the role of TTX-resistant Na+ currents in inflammatory hyperalgesia; implications of three of these questions are discussed.