Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Ave, Box 8054, St. Louis, MO, 63110, USA.
Washington University Pain Center, Washington University School of Medicine, 660 S. Euclid Ave, Box 8054, St. Louis, MO, 63110, USA.
Nat Commun. 2019 Sep 25;10(1):4356. doi: 10.1038/s41467-019-12316-0.
Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation in mice. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, may encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.
痒是一种明显的厌恶性感觉，会引起强烈的搔抓欲望。尽管我们最近对痒的外周基础有了更多的了解，但对于中枢神经回路如何调节急性和慢性痒觉处理，我们知之甚少。在这里，我们确定了在小鼠中，特定的导水管周围灰质（periaqueductal gray，PAG）神经元群体在痒觉调制中的因果贡献。化学遗传操作表明 PAG 中的神经元对搔抓具有双向调制作用。光纤光度测定研究表明，在氯喹诱发的搔抓过程中，PAG 中的 GABA 能和谷氨酸能神经元的活动以相反的方式被调制。此外，PAG GABA 能神经元的激活或谷氨酸能神经元的抑制均可导致急性和慢性瘙痒中搔抓的减少。令人惊讶的是，PAG GABA 能神经元，而不是谷氨酸能神经元，可能编码痒觉的厌恶性成分。因此，PAG 代表了一个神经调节中枢，调节急性和慢性痒觉的感觉和情感方面。
