Department of Neuroscience, Uppsala University, Box 593, 751 24 Uppsala, Sweden.
Neuron. 2010 Nov 4;68(3):529-42. doi: 10.1016/j.neuron.2010.09.016.
The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.
对瘙痒感觉的自然反应是搔抓，这通过一种未知的机制缓解了瘙痒。疼痛和瘙痒之间的相互作用已经得到了频繁的证明，基于电生理和行为实验数据的瘙痒选择性假说假设存在能够抑制瘙痒的原发性疼痛传入。在这里，我们证明了在与香草素受体 (TRPV1) 初级传入纤维部分重叠的神经元亚群中删除囊泡谷氨酸转运蛋白 (VGLUT) 2 会导致瘙痒行为显著增加，同时对热痛的反应性降低。抗组胺药物的给药和胃泌素释放肽受体的基因缺失减少了瘙痒行为的增加，这表明 VGLUT2 依赖于组胺能和非组胺能瘙痒来维持正常水平。这项研究确立了 VGLUT2 是 TRPV1 热伤害感受的主要参与者，也有助于调节正常的瘙痒反应。
