Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.
Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.
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DOI：
10.1167/iovs.62.14.15
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发表时间：
2021-11-01
影响因子：
4.4
通讯作者：
Meng ID
中科院分区：
文献类型：
--
作者：
Mecum NE;Russell R;Lee J;Sullivan C;Meng ID
本研究的目的是探讨表达Nav1.8的角膜传入神经元在泪腺切除术（LGE）引起的干眼症中持续疼痛的作用。在Nav1.8-cre小鼠角膜内事件中，质子泵archaerhodopin -3/eGFP （ArchT/eGFP）有条件表达。单侧LGE引起干眼。实时位置偏好评估使用三室仪器。在一个中性的、没有照明的中央房间的两侧，有一个被控制灯照亮，另一个被ArchT激活灯照亮。对于实时偏好，研究人员将动物置于中性室，并在五次10分钟的会议中进行跟踪，在第二和第四次会议中打开灯。在另一项研究中，动物的运动被跟踪了三次，每次10分钟（只在第二次会议上开灯），在4天的过程中每天测试一次。局部麻醉用于检查正在进行的角膜传入活动在产生位置偏好中的作用。在Nav1.8-cre中，角膜传入神经和三叉神经节细胞体显示出强烈的eGFP信号；ArchT / eGFP老鼠。LGE后，Nav1.8-cre；ArchT/eGFP小鼠表现出对ArchT激活光配对室的偏好。预先应用于角膜的局部麻醉剂可以防止偏爱。Nav1.8-cre;假手术的ArchT/eGFP小鼠和LGE野生型对照小鼠没有出现偏好。结果表明，大剂量肾上腺素诱导的持续疼痛是由表达Nav1.8的角膜事件驱动的。抑制这些神经元代表了治疗干眼引起的持续疼痛的潜在策略。
The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain.
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影响因子：
8.8
作者：
Binshtok AM;Gerner P;Oh SB;Puopolo M;Suzuki S;Roberson DP;Herbert T;Wang CF;Kim D;Chung G;Mitani AA;Wang GK;Bean BP;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
7.4
作者：
Boada DM;Martin TJ;Peters CM;Hayashida K;Harris MH;Houle TT;Boyden ES;Eisenach JC;Ririe DG
通讯作者：
Ririe DG
DOI：
10.1016/s0008-4182(04)80071-1
发表时间：
2004-12-01
影响因子：
4.2
作者：
Adatia, FA;Michaeli-Cohen, A;Slomovic, A
通讯作者：
Slomovic, A
影响因子：
16.2
作者：
Arcourt, Alice;Gorham, Louise;Lechner, Stefan G.
通讯作者：
Lechner, Stefan G.
影响因子：
2
作者：
Li, Na;Deng, Xinguo;Zhao, Dongqing
通讯作者：
Zhao, Dongqing