Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice.
Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice.
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DOI：
10.1038/nbt.2834
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发表时间：
2014-03
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
--
作者：
初级伤害性感受器是参与调节正常和病理性疼痛的复杂处理系统的第一批神经元。我们兴奋和抑制这些神经元的能力受到药理学和电刺激的限制；在自由活动的非转基因动物中，非侵入性地兴奋和抑制这些神经元是不可能的。在这里，我们使用光遗传策略来双向控制非转基因小鼠的伤害感受器。坐骨神经内注射编码兴奋性视神经的腺相关病毒，能够通过光诱导刺激急性疼痛、位置厌恶和光基因介导的对机械和热刺激的戒断阈值的降低。相反，病毒传递抑制性视蛋白能够通过光诱导抑制急性痛觉，并逆转神经病理性疼痛模型中的机械性痛觉异常和热痛觉过敏。光是经皮传递的，能够在自由活动的动物身上诱导出这些行为。这种方法可能在基础和转化性疼痛研究中有用，并使快速药物筛选和新设计的Opsins测试成为可能。
Primary nociceptors are the first neurons involved in the complex processing system that regulates normal and pathological pain. Our ability to excite and inhibit these neurons has been limited by pharmacological and electrical stimulation constraints; non-invasive excitation and inhibition of these neurons in freely moving non-transgenic animals has not been possible. Here we use an optogenetic strategy to bidirectionally control nociceptors of non-transgenic mice. Intra-sciatic nerve injection of adeno-associated viruses encoding an excitatory opsin enabled light-inducible stimulation of acute pain, place aversion, and optogenetically mediated reductions in withdrawal thresholds to mechanical and thermal stimuli. In contrast, viral delivery of an inhibitory opsin enabled light-inducible inhibition of acute pain perception, and reversed mechanical allodynia and thermal hyperalgesia in a model of neuropathic pain. Light was delivered transdermally enabling these behaviors to be induced in freely moving animals. This approach may have utility in basic and translational pain research, and enable rapid drug screening and testing of newly engineered opsins.
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影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
25
作者：
Lin, John Y.;Knutsen, Per Magne;Muller, Arnaud;Kleinfeld, David;Tsien, Roger Y.
通讯作者：
Tsien, Roger Y.
影响因子：
17.1
作者：
Chow, Brian Y.;Boyden, Edward S.
通讯作者：
Boyden, Edward S.
影响因子：
64.8
作者：
Yizhar, Ofer;Fenno, Lief E.;Prigge, Matthias;Schneider, Franziska;Davidson, Thomas J.;O'Shea, Daniel J.;Sohal, Vikaas S.;Goshen, Inbal;Finkelstein, Joel;Paz, Jeanne T.;Stehfest, Katja;Fudim, Roman;Ramakrishnan, Charu;Huguenard, John R.;Hegemann, Peter;Deisseroth, Karl
通讯作者：
Deisseroth, Karl