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      Ocular Surface Pain: A Narrative Review

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          Abstract

          Ocular surface pain is a frequent cause of visits to an eye care provider and has a substantial impact on healthcare cost, yet a complete understanding of its causative factors and tools for diagnostic workup are notably missing in many eye clinics. The cornea has the densest sensory innervation in the human body and has the potential to be a powerful producer of pain. Pain can manifest as a result of a noxious stimulus or disruption in the ocular surface anatomy (nociceptive pain), or it can result from abnormalities in the ocular surface neurosensory apparatus itself (neuropathic pain). Novel advances in neurobiology have sought to differentiate the two entities, particularly to identify when chronic dry eye symptomatology is driven by neuropathic ocular pain. In this review, we seek to provide an overview of the prevalence, physiologic factors, and management of ocular surface pain complaints.

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          Nociceptors: the sensors of the pain pathway.

          Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics.
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            Corneal nerves: structure, contents and function

            Experimental Eye Research, 76(5), 521-542
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              Models and mechanisms of hyperalgesia and allodynia.

              Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in their own right. Considerable progress has been made in developing clinically relevant animal models for identifying the most significant underlying mechanisms. This review deals with experimental models that are currently used to measure (sect. II) or to induce (sect. III) hyperalgesia and allodynia in animals. Induction and expression of hyperalgesia and allodynia are context sensitive. This is discussed in section IV. Neuronal and nonneuronal cell populations have been identified that are indispensable for the induction and/or the expression of hyperalgesia and allodynia as summarized in section V. This review focuses on highly topical spinal mechanisms of hyperalgesia and allodynia including intrinsic and synaptic plasticity, the modulation of inhibitory control (sect. VI), and neuroimmune interactions (sect. VII). The scientific use of language improves also in the field of pain research. Refined definitions of some technical terms including the new definitions of hyperalgesia and allodynia by the International Association for the Study of Pain are illustrated and annotated in section I.
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                Author and article information

                Contributors
                agalor@med.miami.edu
                Journal
                Ophthalmol Ther
                Ophthalmol Ther
                Ophthalmology and Therapy
                Springer Healthcare (Cheshire )
                2193-8245
                2193-6528
                5 June 2020
                5 June 2020
                September 2020
                : 9
                : 3
                : 1-21
                Affiliations
                [1 ]GRID grid.484420.e, Surgical Services, , Miami Veterans Affairs Medical Center, ; Miami, FL USA
                [2 ]GRID grid.26790.3a, ISNI 0000 0004 1936 8606, Bascom Palmer Eye Institute, , University of Miami, ; Miami, FL USA
                Author information
                http://orcid.org/0000-0002-3026-6155
                Article
                263
                10.1007/s40123-020-00263-9
                7406607
                32500435
                24c0de36-ed8b-4279-96cf-17aa8062d243
                © The Author(s) 2020

                This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 7 May 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000738, U.S. Department of Veterans Affairs;
                Award ID: CX002015
                Award ID: BX004893
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: R01EY026174
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: GW190010
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: P30EY014801
                Funded by: FundRef http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                dry eye,neuropathic pain,nociceptive pain,ocular pain,ocular surface pain

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