The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nat Neurosci. 2013 Feb;16(2):174-82. doi: 10.1038/nn.3289. Epub 2012 Dec 23.
Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. We genetically labeled and manipulated MrgprA3(+) neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3(+) neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3(+) neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3(+) neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.
几十年来，人们一直在寻找专门的痒觉神经元。最近，由于观察到介导瘙痒的神经元也对疼痛刺激有反应，因此这些神经元是否存在受到了质疑。我们通过基因标记和操作背根神经节（DRG）中的 MrgprA3(+)神经元，发现它们专门支配皮肤的表皮，并对多种瘙痒原产生反应。MrgprA3(+)神经元的消融导致多种瘙痒原引起的搔抓反应显著减少，并在慢性瘙痒条件下自发发生，而疼痛敏感性保持完整。值得注意的是，在 MrgprA3(+)神经元中特异性表达 TRPV1 的小鼠对辣椒素表现出瘙痒而非疼痛行为。虽然 MrgprA3(+)神经元对有害热敏感，但有害热激活这些神经元中的 TRPV1 不会改变疼痛行为。这些数据表明，MrgprA3 定义了介导瘙痒的特定 DRG 神经元亚群。我们的研究为研究瘙痒和开发止痒疗法开辟了新途径。
