Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons.
Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons.
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DOI：
10.1038/s41467-018-04049-3
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发表时间：
2018-04-24
影响因子：
16.6
通讯作者：
Heppenstall PA
中科院分区：
文献类型：
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作者：
Dhandapani R;Arokiaraj CM;Taberner FJ;Pacifico P;Raja S;Nocchi L;Portulano C;Franciosa F;Maffei M;Hussain AF;de Castro Reis F;Reymond L;Perlas E;Garcovich S;Barth S;Johnsson K;Lechner SG;Heppenstall PA
机械性异常性疼痛是神经性疼痛的主要症状，无害的触摸会引起剧烈疼痛。在这里，我们鉴定了一群表达 TrkB 的外周感觉神经元，这些神经元对于小鼠神经损伤后轻触产生疼痛是必要且充分的。表达 TrkB-Cre 的神经元被消融的小鼠在基础条件下对最轻的触摸不太敏感，并且在神经性疼痛模型中无法产生机械性异常性疼痛。此外，神经损伤后这些神经元的选择性光遗传学激活会引起明显的伤害性行为。使用基于 BDNF（TrkB 配体）的光疗方法，我们对这些神经元进行分子引导激光消融，实现 TrkB 阳性神经元从皮肤的长期回缩，并显着逆转多种类型神经性疼痛的机械异常性疼痛。因此，我们确定了通过轻触传递疼痛的周围神经元，并揭示了治疗其的新药理学策略。有几类感觉神经元会导致疼痛状态。在这里，作者证明，TrkB+ 感觉神经元在正常条件下检测小鼠的轻触，但会导致慢性疼痛模型中的超敏反应，而配体引导的激光消融小鼠皮肤中的 TrkB+ 感觉神经元可减弱这种超敏反应。
Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment. There are several classes of sensory neuron that contribute to pain states. Here, the authors demonstrate that TrkB+ sensory neurons detect light touch under normal conditions in mice but contribute to hypersensitivity in models of chronic pain, and that ligand-guided laser ablation of TrkB+ sensory neurons in the mouse skin attenuates this hypersensitivity.
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影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
16.2
作者：
Foster, Edmund;Wildner, Hendrik;Tudeau, Laetitia;Haueter, Sabine;Ralvenius, William T.;Jegen, Monika;Johannssen, Helge;Hoesli, Ladina;Haenraets, Karen;Ghanem, Alexander;Conzelmann, Karl-Klaus;Boesl, Michael;Zeilhofer, Hanns Ulrich
通讯作者：
Zeilhofer, Hanns Ulrich
影响因子：
2.5
作者：
Garrison, Sheldon R.;Dietrich, Alexander;Stucky, Cheryl L.
通讯作者：
Stucky, Cheryl L.
影响因子：
16.2
作者：
Arcourt, Alice;Gorham, Louise;Lechner, Stefan G.
通讯作者：
Lechner, Stefan G.
DOI：
10.1038/jid.2009.176
发表时间：
2009-12
期刊：
The Journal of investigative dermatology
影响因子：
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作者：
通讯作者：
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