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Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain.


ABSTRACT: 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 NaCl). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or topically (eye drop, 100 ?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.

SUBMITTER: Cho J 

PROVIDER: S-EPMC6436610 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain.

Cho Jooyoung J   Bell Nicholas N   Botzet Gregory G   Vora Paras P   Fowler Benjamin J BJ   Donahue Renee R   Bush Heather H   Taylor Bradley K BK   Albuquerque Romulo J C RJC  

Translational vision science & technology 20190326 2


<h4>Purpose</h4>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.<h4>Methods</h4>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 evaluate  ...[more]

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