Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation
Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation
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从外侧臂旁核到外侧和腹外侧导水管周围灰色亚区域的投射介导瘙痒感
DOI：
10.1097/j.pain.0000000000002193
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发表时间：
2021-06-01
期刊：
影响因子：
7.4
通讯作者：
Li, Yun-Qing
中科院分区：
文献类型：
--
作者：
Li, Jia-Ni;Ren, Jia-Hao;Li, Yun-Qing
中脑导水管周围灰质外侧和腹外侧亚区（Lateral and ventral lateral subregions of the periaqueductal gray，l/vlPAG）已被证明是瘙痒处理下行回路的关键组成部分，其作用与被冥想神经元的亚分类有关。本研究以臂旁外侧核（lateral parabrachial nucleus，LPB）为传入核，探讨接受LPB投射的l/vlPAG神经元的调制作用。使用解剖学示踪、化学发生学、光遗传学和局部药理学方法来研究LPB-1/vlPAG通路在小鼠中的痒和疼痛感觉中的参与。首先，已经提供了从LPB中含有囊泡谷氨酸转运蛋白-2的神经元到参与瘙痒传递的l/vlPAG的投射的形态学证据。此外，LPB-1/vlPAG途径的化学遗传学和光遗传学激活导致抗过敏作用和镇痛作用，而药物遗传学抑制增强伤害性感知而不影响自发抓挠行为。最后，将体内药理学与光遗传学相结合，揭示了l/vlPAG中表达AMPA受体的神经元可能在通路调节中发挥更重要的作用。这些发现为LPB和l/vlPAG在痛觉和伤害性感觉中的联系提供了新的认识，并通过选择LPB作为上行传出投射的来源，加深了对l/vlPAG在瘙痒感觉中调节作用的理解。
Lateral and ventral lateral subregions of the periaqueductal gray (l/vlPAG) have been proved to be pivotal components in descending circuitry of itch processing, and their effects are related to the subclassification of neurons that were meditated. In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. First, morphological evidence for projections from vesicular glutamate transporter-2-containing neurons in the LPB to l/vlPAG involved in itch transmission has been provided. Furthermore, chemogenetic and optogenetic activation of the LPB-l/vlPAG pathway resulted in both antipruritic effect and analgesic effect, whereas pharmacogenetic inhibition strengthened nociceptive perception without affecting spontaneous scratching behavior. Finally, in vivo pharmacology was combined with optogenetics which revealed that AMPA receptor-expressing neurons in l/vlPAG might play a more essential role in pathway modulation. These findings provide a novel insight about the connections between 2 prominent transmit nuclei, LPB and l/vlPAG, in both pruriceptive and nociceptive sensations and deepen the understanding of l/vlPAG modulatory roles in itch sensation by chosen LPB as source of ascending efferent projections.