TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease.
TRPM8: A Therapeutic Target for Neuroinflammatory Symptoms Induced by Severe Dry Eye Disease.
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DOI：
10.3390/ijms21228756
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发表时间：
2020-11-19
影响因子：
5.6
通讯作者：
Mélik Parsadaniantz S
中科院分区：
文献类型：
--
作者：
Fakih D;Baudouin C;Réaux-Le Goazigo A;Mélik Parsadaniantz S
干眼病（DED）通常与眼表炎症和疼痛有关。在这项研究中，我们评估了反复注射瞬态受体电位美拉他汀8 （TRPM8）离子通道拮抗剂M8-B对眶外泪腺和哈德氏腺切除引起的严重DED小鼠模型的有效性。术后第7天至第21天，每天局部给予M8-B两次。第21天监测角膜冷、机械敏感性和自发性眼痛。然后通过电生理多单元细胞外记录评估正在进行和冷诱发的纤毛神经活动。在三叉神经节中评估角膜炎症和神经性疼痛和炎症相关基因的表达。我们发现，DED小鼠出现了与三叉神经节（TG）中较高的TRPM8 mRNA表达一致的冷异常性疼痛。慢性M8-B灌注明显逆转了角膜机械性异常痛和自发性眼痛，通常与持续性DED相关。M8-B的注射也减少了DED小鼠持续自发和冷诱发的睫状神经活动，以及角膜和TG的炎症。总的来说，我们的研究为TRPM8阻断对减轻重度DED相关角膜疼痛综合征的有效性提供了新的见解，为眼部疼痛管理开辟了新的途径。
Dry eye disease (DED) is commonly associated with ocular surface inflammation and pain. In this study, we evaluated the effectiveness of repeated instillations of transient receptor potential melastatin 8 (TRPM8) ion channel antagonist M8-B on a mouse model of severe DED induced by the excision of extra-orbital lacrimal and Harderian glands. M8-B was topically administered twice a day from day 7 until day 21 after surgery. Cold and mechanical corneal sensitivities and spontaneous ocular pain were monitored at day 21. Ongoing and cold-evoked ciliary nerve activities were next evaluated by electrophysiological multi-unit extracellular recording. Corneal inflammation and expression of genes related to neuropathic pain and inflammation were assessed in the trigeminal ganglion. We found that DED mice developed a cold allodynia consistent with higher TRPM8 mRNA expression in the trigeminal ganglion (TG). Chronic M8-B instillations markedly reversed both the corneal mechanical allodynia and spontaneous ocular pain commonly associated with persistent DED. M8-B instillations also diminished the sustained spontaneous and cold-evoked ciliary nerve activities observed in DED mice as well as inflammation in the cornea and TG. Overall, our study provides new insight into the effectiveness of TRPM8 blockade for alleviating corneal pain syndrome associated with severe DED, opening a new avenue for ocular pain management.
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DOI：
10.1016/j.jtos.2016.09.004
发表时间：
2017-01
期刊：
The ocular surface
影响因子：
--
作者：
Cruzat A;Qazi Y;Hamrah P
通讯作者：
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影响因子：
64.8
作者：
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影响因子：
4.4
作者：
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影响因子：
7.3
作者：
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Brandolini, Laura
影响因子：
16.2
作者：
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通讯作者：
Qin, Ning