Department of Biological Structure, University of Washington, Seattle, United States.
Graduate Program in Neuroscience, University of Washington, Seattle, United States.
Elife. 2018 Mar 21;7:e32036. doi: 10.7554/eLife.32036.
Little is known about the capacity of lower vertebrates to experience itch. A screen of itch-inducing compounds (pruritogens) in zebrafish larvae yielded a single pruritogen, the TLR7 agonist imiquimod, that elicited a somatosensory neuron response. Imiquimod induced itch-like behaviors in zebrafish distinct from those induced by the noxious TRPA1 agonist, allyl isothiocyanate. In the zebrafish, imiquimod-evoked somatosensory neuronal responses and behaviors were entirely dependent upon TRPA1, while in the mouse TRPA1 was required for the direct activation of somatosensory neurons and partially responsible for behaviors elicited by this pruritogen. Imiquimod was found to be a direct but weak TRPA1 agonist that activated a subset of TRPA1 expressing neurons. Imiquimod-responsive TRPA1 expressing neurons were significantly more sensitive to noxious stimuli than other TRPA1 expressing neurons. Together, these results suggest a model for selective itch via activation of a specialized subpopulation of somatosensory neurons with a heightened sensitivity to noxious stimuli.
目前对于低等脊椎动物感受瘙痒的能力知之甚少。在斑马鱼幼虫中筛选致痒化合物（致痒原），得到了一种致痒原，即 TLR7 激动剂咪喹莫特，它能引起感觉神经元反应。咪喹莫特在斑马鱼中引起的瘙痒样行为不同于有害的 TRPA1 激动剂丙烯基异硫氰酸酯引起的行为。在斑马鱼中，咪喹莫特引起的感觉神经元反应和行为完全依赖于 TRPA1，而在小鼠中，TRPA1 是直接激活感觉神经元所必需的，并且部分负责由这种致痒原引起的行为。研究发现，咪喹莫特是一种直接但较弱的 TRPA1 激动剂，可激活一组表达 TRPA1 的神经元。对咪喹莫特有反应的表达 TRPA1 的神经元对有害刺激的敏感性明显高于其他表达 TRPA1 的神经元。总之，这些结果表明了一种通过激活对有害刺激具有更高敏感性的特定感觉神经元亚群来选择性产生瘙痒的模型。
