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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]

PMID: 30937216

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Project description:Objective This paper reviews ocular pain with the main focus on ocular surface discomfort and dry eye pain. Anatomy, physiology, epidemiology, assessment, and treatment are discussed in this paper. Methods A PubMed search was conducted for studies published from 2000 to 2019 on the anatomy, pathophysiology, epidemiology, assessment, and treatment of ocular pain. Reviews, meta-analyses, and randomized clinical trials were included. Inclusion criteria focused on ocular surface discomfort, dry eye pain and neuropathic pain. Results A total of 112 articles were found through searches, 45 of which were selected and studied in this review. Discussion Pain in general can be acute or chronic. Acute pain is usually a physiologic response to a serious damage to the tissues and alleviates with pain relief treatments. Chronic pain is defined as the persistence of pain for more than three months. From another point of view, pain has been classified into either nociceptive or neuropathic. Nociceptive pain is a physiologic response to a noxious stimulus. Both central and peripheral nervous systems can be involved in the development of a neuropathic pain, which is characterized by positive or negative sensory signs, a pain perceived disproportionate to a noxious stimulus, and/or not responsive to analgesics. Chronic pain usually has a neuropathic component. Ocular surface pain is a well-known complaint after any corneal surgery. This is mainly due to abnormal regeneration of damaged corneal nerve endings and abnormal connections with adjacent nerve endings which produce spontaneous activity. Tear hyperosmolarity and the resultant ocular surface inflammation can also trigger voluntary activity of corneal nerve endings. Referral pain to the first and second division of the trigeminal nerve has been reported. Interference with vision and even sleep, which is out of proportion to the examination are among patients’ complaints. All of these elements proposed the new concept of ocular neuropathic pain syndrome. The first step in conventional evaluation of ocular discomfort is search for tear insufficiency. Pathologies of lid and blinking as well as conjunctival irregularities should be addressed. Anti-inflammatory agents and, in resistant cases, systemic neuromodulators are shown to be helpful. Education on behavioral changes and reassurance are essential steps. Considering the neuropathic origin for the ocular pain, treatment modalities used for such pain in other parts of the body can be considered for this syndrome.

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Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain.

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Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain.

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