Uncontrollable itch-scratching cycles lead to serious skin damage in patients with chronic itch. However, the neural mechanism promoting the itch-scratching cycle remains elusive. Here, we report that tachykinin 1 (Tac1)-expressing glutamatergic neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) facilitate the itch-scratching cycle. We found that l/vlPAG neurons exhibited scratching-behavior-related neural activity and that itch-evoked scratching behavior was impaired after suppressing the activity of l/vlPAG neurons. Furthermore, we showed that the activity of Tac1-expressing glutamatergic neurons in the l/vlPAG was elevated during itch-induced scratching behavior and that ablating or suppressing the activity of these neurons decreased itch-induced scratching behavior. Importantly, activation of Tac1-expressing neurons induced robust spontaneous scratching and grooming behaviors. The scratching behavior evoked by Tac1-expressing neuron activation was suppressed by ablation of spinal neurons expressing gastrin-releasing peptide receptor (GRPR), the key relay neurons for itch. These results suggest that Tac1-expressing neurons in the l/vlPAG promote itch-scratching cycles.

中文翻译：

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Tac1表达的神经元在水管前灰色中通过递减调节促进瘙痒-抓痒循环。

慢性瘙痒患者无法控制的抓痒周期会严重损害皮肤。但是，促进痒痒循环的神经机制仍然难以捉摸。在这里，我们报告说速激肽1（Tac1）在外侧和腹侧导水管周围灰色（l / vlPAG）中表达谷氨酸能神经元促进瘙痒抓痒周期。我们发现l / vlPAG神经元表现出与抓挠行为相关的神经活动，并且在抑制l / vlPAG神经元的活动后，痒痒的抓挠行为受到损害。此外，我们发现在l / vlPAG中表达Tac1的谷氨酸能神经元的活性在瘙痒诱导的scratch抓行为中升高，而消融或抑制这些神经元的活性降低了瘙痒诱导的scratch抓行为。重要的，Tac1表达神经元的激活诱导强大的自发性抓挠和修饰行为。Tac1表达神经元激活引起的抓行为被表达胃泌素释放肽受体（GRPR）的脊髓神经元消融所抑制，GRPR是瘙痒的关键中继神经元。这些结果表明，l / vlPAG中表达Tac1的神经元促进痒痒循环。