Role of 5-HT1A and 5-HT3 receptors in serotonergic activation of sensory neurons in relation to itch and pain behavior in the rat.

Role of 5-HT1A and 5-HT3 receptors in serotonergic activation of sensory neurons in relation to itch and pain behavior in the rat.
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DOI:
10.1002/jnr.24633
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发表时间:
2020-10
影响因子:
4.2
通讯作者:
Babes A
Babes A
中科院分区:
医学3区
文献类型:
--
作者:
Domocos D;Selescu T;Ceafalan LC;Iodi Carstens M;Carstens E;Babes A

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由血小板、肥大细胞和免疫细胞释放的5-羟色胺(5-HT)是一种有效的炎症介质,可调节外周神经系统的疼痛和瘙痒感测。参与这些感觉功能的初级传入神经元表达的多巴胺能受体尚未完全确定,并且似乎在很大程度上具有种属依赖性。此外,5-HT受体激活与神经元兴奋性变化相结合的机制尚未完全揭示。使用在体外(钙和电压成像和膜片钳)和在体内的行为方法相结合,我们使用雄性和雌性Wistar大鼠提供证据的参与两个5-HT受体亚型,5-HT 1A和5-HT 3,在介导的持续和短暂的影响,分别,5-HT对大鼠初级传入神经元参与疼痛和瘙痒处理。此外,我们的研究结果是一致的模型,其中持续通过5-HT 1A受体触发的多巴胺能反应是由于背景钾通道的关闭,然后通过膜去极化和动作电位,在此期间,电压门控钙通道的激活导致钙离子进入。我们的研究结果可能会提供一个更好的理解哺乳动物的神经刺激性瘙痒信号。
Serotonin (5-hydroxytryptamine, 5-HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5-HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch-clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5-HT receptor subtypes, 5-HT1A and 5-HT3, in mediating the sustained and transient effects, respectively, of 5-HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5-HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage-gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling.
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