Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain
Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain
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DOI：
10.1167/tvst.8.2.6
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发表时间：
2019-03-01
影响因子：
3
通讯作者：
Albuquerque, Romulo J. C.
中科院分区：
文献类型：
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作者：
Cho, Jooyoung;Bell, Nicholas;Albuquerque, Romulo J. C.
目的：慢性眼痛是一种鲜为人知且难以治疗的疾病。我们建立了一个小鼠角膜表面损伤（CSI）引起的慢性眼神经性疼痛模型。该研究的重点是CSI后角膜神经形态学的变化和相关的短期和长期疼痛样行为。方法：局部应用0.75 N NaOH碱溶液诱导小鼠CSI。观察角膜神经的结构、形态、密度和长度。观察高渗盐水（2 M NaCI）治疗前后擦眼效果。给予阿片受体拮抗剂纳曲酮（NTX）或纳洛酮-甲氧基醚（NLX-me）皮下（s.c c, 3 mg/kg）或局部（滴眼液，100 μ M），然后进行擦眼试验。结果：CSI引起部分角膜神经失支配，然后逐渐恢复。再生的神经显示出增加的扭曲、串珠和分支。与基线或假损伤相比，CSI增强了高渗盐水诱导的擦眼行为（P < 0.01）。这种超敏反应在CSI后第10天达到高峰，第14天消退。给药NTX或NLX-me，一种选择性外周阿片拮抗剂，恢复了损伤组的擦眼行为，但在假手术组没有（P < 0.05）。结论：本研究建立了CSI术后慢性眼痛和角膜神经病变的模型。CSI诱导中枢和外周阿片受体依赖的潜在致敏（LS），这是通过全身或局部施用阿片拮抗剂来揭示的。翻译意义：该慢性眼痛模型确立了LS在眼三叉神经系统中是一种新的抑制机制，并可能用于眼神经病变的潜在诊断和治疗干预。
Purpose: Chronic ocular pain is poorly understood and difficult to manage. We developed a murine model of corneal surface injury (CSI)-induced chronic ocular neuropathic pain. The study focuses on changes in corneal nerve morphology and associated short- and long-term pain-like behavior after CSI.Methods: CSI was induced in mice by local application of an alkali solution (0.75 N NaOH). Corneal nerve architecture, morphology, density, and length were studied. Eye-wiping was evaluated before and after CSI in response to hypertonic saline (2 M NaCI). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or topically (eye drop, 100 mu M), and then an eye-wiping test was performed.Results: CSI caused partial corneal deinnervation followed by gradual reinnervation. Regenerated nerves displayed increased tortuosity, beading, and branching. CSI enhanced hypertonic saline-induced eye-wiping behavior compared to baseline or sham-injury (P < 0.01). This hypersensitivity peaked at 10 days and subsided 14 days after CSI. Administration of NTX, or NLX-me, a selective peripheral opioid antagonist, reinstated eye-wiping behavior in the injury group, but not in the sham groups (P < 0.05).Conclusions: This study introduces a model of chronic ocular pain and corneal neuropathy following CSI. CSI induces central and peripheral opioid receptor-dependent latent sensitization (LS) that is unmasked by systemic or topical administration of opioid antagonists.Translational Relevance: This model of chronic ocular pain establishes LS as a new inhibitory mechanism in the oculotrigeminal system and may be used for potential diagnostic and therapeutic interventions for ocular neuropathy.