The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors
The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors
复制标题
DOI：
10.1523/jneurosci.22-03-01010.2002
复制
发表时间：
2002-02-01
影响因子：
5.3
通讯作者：
Basbaum, AI
中科院分区：
文献类型：
--
作者：
Zeitz, KP;Guy, N;Basbaum, AI
血清素是炎症化学环境的主要组成部分，通过对多种受体亚型的作用，有助于组织损伤的疼痛。在这里，我们研究了遗传或药物破坏5-HT3受体后的小鼠，5-HT3受体是一种兴奋的5-羟色胺门控离子通道。我们证明，组织损伤诱导的持续性，但不是急性，痛觉显著减少后，该受体亚型的功能消除。具体来说，在组织损伤的情况下，5-HT3受体介导伤害感受器的激活，但不会导致损伤相关性水肿。这一结果可以解释为5-HT3受体转录本定位于先前未表征的有髓和无髓传入神经事件亚群，其中很少表达促炎神经肽p物质。最后，我们提供证据表明，中枢5-羟色胺能回路通过促进脊髓5-HT3受体的作用来调节伤害性传递。我们得出结论，外周和中枢5-HT3受体的激活都是前知觉，外周5-HT3受体的作用涉及初级传入伤害感受器的新补体。
Serotonin is a major component of the inflammatory chemical milieu and contributes to the pain of tissue injury via an action on multiple receptor subtypes. Here we studied mice after genetic or pharmacological disruption of the 5-HT3 receptor, an excitatory serotonin-gated ion channel. We demonstrate that tissue injury-induced persistent, but not acute, nociception is significantly reduced after functional elimination of this receptor subtype. Specifically, in the setting of tissue injury, the 5-HT3 receptor mediates activation of nociceptors but does not contribute to injury-associated edema. This result is explained by the localization of 5-HT3 receptor transcripts to a previously uncharacterized subset of myelinated and unmyelinated afferents, few of which express the proinflammatory neuropeptide substance P. Finally, we provide evidence that central serotonergic circuits modulate nociceptive transmission via a facilitatory action at spinal 5-HT3 receptors. We conclude that activation of both peripheral and central 5-HT3 receptors is pronociceptive and that the contribution of peripheral 5-HT3 receptors involves a novel complement of primary afferent nociceptors.