Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States.

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States.
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大体感神经元不同类型兴奋性的表征及其在病理疼痛状态下的塑性变化。

DOI:
10.3390/ijms19010161
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发表时间:
2018-01-05
影响因子:
5.6
通讯作者:
Luo C
Luo C
中科院分区:
生物学2区
文献类型:
--
作者:
Xie RG;Chu WG;Hu SJ;Luo C

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感觉神经元类型已通过不同的形态学和转录特征来区分。兴奋性是神经元最基本的功能特征。霍奇金描述的数学模型根据放电频率和施加电流强度之间的关系揭示了三种类型的神经元兴奋性。然而,天然感觉神经元是否表现出不同的功能特性,在兴奋性和这种兴奋性类型是否经历病理性疼痛状态下的可塑性变化仍然是难以捉摸的。在这里,我们利用全细胞膜片钳记录,行为和药理学分析,我们证明,大背根神经节(DRG)神经元可以分为3类和4个亚类的兴奋模式的基础上,这是类似的数学模型提出的霍奇金。超极化激活的阳离子电流(Ih)的分析表明,不同的兴奋性类型的大DRG神经元的Ih的大小不同,与更高的Ih在2 - 1类比在1,2 - 2和3类。这表明Ih在决定DRG大神经元兴奋性类型中起着重要作用。更重要的是,这种兴奋模式在周围神经损伤引起的病理性疼痛状态下表现出可塑性变化和过渡。本研究揭示了大DRG神经元的功能特征,并通过整合转录组学和形态学特征扩展了大DRG神经元的功能分类。
Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics.
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