引用

慢性疼痛和瘙痒折磨着数百万患者，目前的治疗在很大程度上是无效的。疼痛和瘙痒的神经控制尚未完全阐明，这限制了针对潜在神经回路的治疗方法的发展。感觉信息从末梢神经传递到脊髓，再向上传递到大脑(自下而上的通路)，但也可以通过大脑到脊髓的自上而下的投射来调节。然而，介导自上而下的疼痛抑制的神经元还没有完全阐明，也没有任何这样的途径被确定为瘙痒感觉。在这里，我们在脑干腹侧发现了一种新的gaba能神经元，通过前啡肽的表达来区分。我们将其命名为LJA5，以描述其在侧脑桥中的位置，并与A5细胞群并列。LJA5神经元向脊髓提供了唯一已知的选择性靶向椎板I的抑制投射，它专门向大脑传递疼痛、温度和瘙痒信息。通过这项工作，我们试图研究LJA5神经元在感觉中的作用。第一个设置的实验旨在更全面地描述LJA5神经元。我们首先确定了小鼠的基因表达模式，然后我们在人类大脑中寻找这些神经元。 We then fully explored the input and output connections of LJA5 neurons in mouse using anterograde and retrograde tracers. These neurons demonstrate the first inhibitory projection specifically targeting lamina I of the spinal cord. This finding, along with projections to other sensory regions in the brainstem, suggested that LJA5 neurons directly inhibit noxious sensory information. Furthermore, we show that LJA5 neurons receive input from forebrain structures implicated in stress and sensory detection. In the second set of experiments, we tested the function of LJA5 neurons through chemogenetic activation during behavioral tests. We knew that LJA5 neurons projected to many known sensory regions including lamina I of the spinal cord, so we hypothesized that LJA5 neurons could modulate itch, pain, or temperature sensations. Chemogenetically activating LJA5 neurons reduced capsaicin-induced pain and histamine-induced itch. Together, our findings identify and characterize a novel nucleus in the brainstem with the first described inhibitory projection specifically targeting lamina I of the spinal cord. Additionally, this is the first identified descending projection that reduces both pain and itch. This new top-down pathway updates current sensory models and opens new treatment opportunities for refractory pain and pruritis.