Capsazepine decreases corneal pain syndrome in severe dry eye disease.
Capsazepine decreases corneal pain syndrome in severe dry eye disease.
复制标题
DOI：
10.1186/s12974-021-02162-7
复制
发表时间：
2021-05-11
影响因子：
9.3
通讯作者：
Parsadaniantz SM
中科院分区：
文献类型：
--
作者：
Fakih D;Guerrero-Moreno A;Baudouin C;Réaux-Le Goazigo A;Parsadaniantz SM
干眼病（DED）是一种伴有神经感觉异常的眼表多因素疾病。在这里，我们评估了瞬时受体电位香草素-1 （TRPV1）阻断对缓解严重DED相关的眼痛、神经炎症和焦虑样行为的有效性。采用单侧切除成年雄性小鼠哈德氏腺和眶外泪腺的方法诱导慢性DED。术后21天进行调查。采用RNAscope原位杂交技术检测三叉神经节（TG）中TRPV1、瞬时受体电位锚蛋白1 （TRPA1）、酸感离子通道1和3 (ASIC1和ASIC3) mRNA表达水平。睫状神经纤维活性的多单元细胞外记录用于监测离体眼部制剂中自发和刺激（冷、热、酸）角膜神经反应。从术后第7天到第21天，DED小鼠每天两次局部注射TRPV1拮抗剂（capsazepine），持续2周。使用全局基因组方法评估TG中涉及神经性和炎症性疼痛的基因表达。观察角膜化学、机械痛觉和自发性眼痛。最后，通过升高加迷宫和黑白盒测试评估焦虑样行为。首先，原位杂交显示，DED可触发TG眼部分支中TRPV1、TRPA1、ASIC1和ASIC3 mRNA的上调。DED还诱导TG中与神经性疼痛和炎症性疼痛相关的基因过表达。在离体眼制剂中，反复滴注辣椒平可降低角膜对热、冷和酸性刺激的多峰反应性。与这些发现一致，慢性辣椒素滴注抑制了DED动物TG中神经性和炎性疼痛相关基因的上调，减少了眼痛的感觉，以及与严重DED相关的焦虑样行为。这些数据为TRPV1拮抗剂灌注缓解严重DED引起的异常角膜神经感觉症状的有效性提供了新的见解，为该分子重新定位为慢性DED患者的潜在镇痛治疗开辟了道路。
Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED. Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests. First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED. These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.
登录
查看更多内容
影响因子：
5.3
作者：
Del Puerto A;Wandosell F;Garrido JJ
通讯作者：
Garrido JJ
影响因子：
5.3
作者：
Du X;Gamper N
通讯作者：
Gamper N
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：
Hamrah P
影响因子：
7.4
作者：
Chen, XJ;Belmonte, C;Rang, HP
通讯作者：
Rang, HP
影响因子：
5.3
作者：
Andreoli M;Marketkar T;Dimitrov E
通讯作者：
Dimitrov E