Visceral and somatic pain serve as protective mechanisms against external threats. Accumulated evidence has confirmed that the paraventricular hypothalamus (PVH) plays an important role in the perception of visceral and somatic pain, whereas the exact neural pathways and molecules distinguishing them remain unclear. Here, we report distinct neuronal ensembles within the PVH dedicated to processing visceral and somatic pain signals. An essential discovery is the distinct expression of P2X3R and VIPR2 in visceral and somatic pain-activated PVH neuronal ensembles. Furthermore, visceral pain- and somatic pain-responsive PVH neuronal ensembles project to specific downstream regions, the ventral part of the lateral septal nucleus (LSV) and the caudal part of the zona incerta (ZIC), respectively. These findings unveil that the PVH acts as a pain sorting center that distinctly processes visceral and somatic pain, identifying potential molecular targets for specific pain processing and providing a new framework for comprehending how the brain processes nociceptive information.

中文翻译：

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室旁下丘脑的不同回路和分子靶点可解码内脏和躯体疼痛


内脏和躯体疼痛是抵御外部威胁的保护机制。积累的证据证实，室旁下丘脑 （PVH） 在内脏和躯体疼痛的感知中起着重要作用，而区分它们的确切神经通路和分子仍不清楚。在这里，我们报道了 PVH 内专门用于处理内脏和躯体疼痛信号的不同神经元集合。一个重要的发现是 P2X3R 和 VIPR2 在内脏和体细胞疼痛激活的 PVH 神经元集合中的独特表达。此外，内脏疼痛和躯体疼痛反应性 PVH 神经元集合分别投射到特定的下游区域，即外侧间隔核 （LSV） 的腹侧部分和不定带 （ZIC） 的尾部。这些发现揭示了 PVH 充当疼痛分类中心，专门处理内脏和躯体疼痛，确定特定疼痛处理的潜在分子靶点，并为理解大脑如何处理伤害性信息提供了一个新框架。