{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:40:34Z","timestamp":1790484034128,"version":"4.1.0"},"reference-count":52,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"2","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Trans. Vis. Sci. Tech."],"published-print":{"date-parts":[[2019,3,26]]},"DOI":"10.1167\/tvst.8.2.6","type":"journal-article","created":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T16:32:37Z","timestamp":1553617957000},"page":"6","source":"Crossref","is-referenced-by-count":28,"title":["Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain"],"prefix":"10.1167","volume":"8","author":[{"given":"Jooyoung","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Botzet","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paras","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, University of Miami Miller, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Donahue","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington, KY, USA"},{"name":"Department of Anesthesiology, University of Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romulo J. C.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i2164-2591-8-2-6-b01","doi-asserted-by":"crossref","unstructured":"Workshop DE. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007; 5: 93\u2013107.","DOI":"10.1016\/S1542-0124(12)70082-4"},{"key":"i2164-2591-8-2-6-b02","doi-asserted-by":"crossref","unstructured":"Galor A, Zlotcavitch L, Walter SD, et al. Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain. Br J Ophthalmol. 2015; 99: 665\u2013668.","DOI":"10.1136\/bjophthalmol-2014-306057"},{"key":"i2164-2591-8-2-6-b03","doi-asserted-by":"crossref","unstructured":"Muller LJ, Marfurt CR, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003; 76: 521\u2013542.","DOI":"10.1016\/S0014-4835(03)00050-2"},{"key":"i2164-2591-8-2-6-b04","doi-asserted-by":"crossref","unstructured":"Dieckmann G, Goyal S, Hamrah P. Neuropathic corneal pain: approaches for management. Ophthalmology. 2017; 124: S34\u2013S47.","DOI":"10.1016\/j.ophtha.2017.08.004"},{"key":"i2164-2591-8-2-6-b05","doi-asserted-by":"crossref","unstructured":"Borsook D, Rosenthal P. Chronic (neuropathic) corneal pain and blepharospasm: five case reports. Pain. 2011; 152: 2427\u20132431.","DOI":"10.1016\/j.pain.2011.06.006"},{"key":"i2164-2591-8-2-6-b06","doi-asserted-by":"crossref","unstructured":"Rosenthal P, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf. 2012; 10: 2\u201314.","DOI":"10.1016\/j.jtos.2012.01.002"},{"key":"i2164-2591-8-2-6-b07","doi-asserted-by":"crossref","unstructured":"Rosenthal P, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016; 100: 128\u2013134.","DOI":"10.1136\/bjophthalmol-2014-306280"},{"key":"i2164-2591-8-2-6-b08","doi-asserted-by":"crossref","unstructured":"Wenk HN, Honda CN. Silver nitrate cauterization: characterization of a new model of corneal inflammation and hyperalgesia in rat. Pain. 2003; 105: 393\u2013401.","DOI":"10.1016\/S0304-3959(03)00295-1"},{"key":"i2164-2591-8-2-6-b09","doi-asserted-by":"crossref","unstructured":"Barabino S, Shen L, Chen L, Rashid S, Rolando M, Dana MR. The controlled-environment chamber: a new mouse model of dry eye. Invest Ophthalmol Vis. Sci. 2005; 46: 2766\u20132771.","DOI":"10.1167\/iovs.04-1326"},{"key":"i2164-2591-8-2-6-b10","unstructured":"Lin Z, Liu X, Zhou T, et al.A mouse dry eye model induced by topical administration of benzalkonium chloride. Mol Vis. 2011; 17: 257\u2013264."},{"key":"i2164-2591-8-2-6-b11","doi-asserted-by":"crossref","unstructured":"Stevenson W, Chen Y, Lee SM, et al. Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease. Cornea. 2014; 33: 1336\u20131341.","DOI":"10.1097\/ICO.0000000000000264"},{"key":"i2164-2591-8-2-6-b12","doi-asserted-by":"crossref","unstructured":"Bian F, Xiao Y, Zaheer M, Volpe EA, Pflugfelder SC, Li DQ, de Paiva CS. Inhibition of NLRP3 inflammasome pathway by butyrate improves corneal wound healing in corneal alkali burn. Int J Mol Sci. 2017: 18 (3).","DOI":"10.3390\/ijms18030562"},{"key":"i2164-2591-8-2-6-b13","unstructured":"Yan ZX, Luo Y, Liu NF. Blockade of angiopoietin-2\/Tie2 signaling pathway specifically promotes inflammation-induced angiogenesis in mouse cornea. Int J Ophthalmol. 2017; 10: 1187\u20131194."},{"key":"i2164-2591-8-2-6-b14","doi-asserted-by":"crossref","unstructured":"Galor A, Batawi H, Felix ER, Margolis TP, Sarantopoulos KD, Martin ER, Levitt RC. Incomplete response to artificial tears is associated with features of neuropathic ocular pain. Br J Ophthalmol. 2016; 100: 745\u2013749.","DOI":"10.1136\/bjophthalmol-2015-307094"},{"key":"i2164-2591-8-2-6-b15","doi-asserted-by":"crossref","unstructured":"Jacobs DS. Diagnosis and treatment of ocular pain: the ophthalmologist's perspective. Curr Ophthalmol Rep. 2017; 5: 271\u2013275.","DOI":"10.1007\/s40135-017-0152-1"},{"key":"i2164-2591-8-2-6-b16","doi-asserted-by":"crossref","unstructured":"Solway B, Bose SC, Corder G, Donahue RR, Taylor BK. Tonic inhibition of chronic pain by neuropeptide Y. Proc Natl Acad Sci U S A. 2011; 108: 7224\u20137229.","DOI":"10.1073\/pnas.1017719108"},{"key":"i2164-2591-8-2-6-b17","doi-asserted-by":"crossref","unstructured":"Corder G, Doolen S, Donahue RR, et al. Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science. 2013; 341: 1394\u20131399.","DOI":"10.1126\/science.1239403"},{"key":"i2164-2591-8-2-6-b18","unstructured":"Ormerod LD, Abelson MB, Kenyon KR. Standard models of corneal injury using alkali-immersed filter discs. Invest Ophthalmol Vis. Sci. 1989; 30: 2148\u20132153."},{"key":"i2164-2591-8-2-6-b19","doi-asserted-by":"crossref","unstructured":"Klocek MS, Sassani JW, McLaughlin J, Zagon IS. Topically applied naltrexone restores corneal reepithelialization in diabetic rats. J Ocul Pharmacol Ther. 2007; 23: 89\u2013102.","DOI":"10.1089\/jop.2006.0111"},{"key":"i2164-2591-8-2-6-b20","doi-asserted-by":"crossref","unstructured":"Albuquerque RJ, Hayashi T, Cho WG, et al. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med. 2009; 15: 1023\u20131030.","DOI":"10.1038\/nm.2018"},{"key":"i2164-2591-8-2-6-b21","doi-asserted-by":"crossref","unstructured":"Zudaire E, Gambardella L, Kurcz C, Vermeren S. A computational tool for quantitative analysis of vascular networks. PLoS One. 2011; 6: e27385.","DOI":"10.1371\/journal.pone.0027385"},{"key":"i2164-2591-8-2-6-b22","doi-asserted-by":"crossref","unstructured":"Launay PS, Godefroy D, Khabou H, et al. Combined 3DISCO clearing method, retrograde tracer and ultramicroscopy to map corneal neurons in a whole adult mouse trigeminal ganglion. Exp Eye Res. 2015; 139: 136\u2013143.","DOI":"10.1016\/j.exer.2015.06.008"},{"key":"i2164-2591-8-2-6-b23","doi-asserted-by":"crossref","unstructured":"Belmonte C, Gallar J, Pozo MA, Rebollo I. Excitation by irritant chemical substances of sensory afferent units in the cat's cornea. J Physiol. 1991; 437: 709\u2013725.","DOI":"10.1113\/jphysiol.1991.sp018621"},{"key":"i2164-2591-8-2-6-b24","doi-asserted-by":"crossref","unstructured":"Marvizon JC, Walwyn W, Minasyan A, Chen W, Taylor BK. Latent sensitization: a model for stress-sensitive chronic pain. Curr Protoc Neurosci. 2015; 71: 9.50.1\u201314.","DOI":"10.1002\/0471142301.ns0950s71"},{"key":"i2164-2591-8-2-6-b25","doi-asserted-by":"crossref","unstructured":"Guan Y, Yuan F, Carteret AF, Raja SN, et al. A partial L5 spinal nerve ligation induces a limited prolongation of mechanical allodynia in rats: an efficient model for studying mechanisms of neuropathic pain. Neurosci Lett. 2010; 471: 43\u201347.","DOI":"10.1016\/j.neulet.2010.01.006"},{"key":"i2164-2591-8-2-6-b26","doi-asserted-by":"crossref","unstructured":"Bargagna-Mohan P, Paranthan RR, Hamza A. Withaferin A targets intermediate filaments glial fibrillary acidic protein and vimentin in a model of retinal gliosis. J Biol Chem. 2010; 285: 7657\u20137669.","DOI":"10.1074\/jbc.M109.093765"},{"key":"i2164-2591-8-2-6-b27","doi-asserted-by":"crossref","unstructured":"Ferrari G, Bignami F, Giacomini C, et al. Ocular surface injury induces inflammation in the brain: in vivo and ex vivo evidence of a corneal-trigeminal axis. Invest Ophthalmol Vis. Sci. 2014; 55: 6289\u20136300.","DOI":"10.1167\/iovs.14-13984"},{"key":"i2164-2591-8-2-6-b28","doi-asserted-by":"crossref","unstructured":"Paschalis EI, Zhou C, Lei F, et al. Mechanisms of retinal damage after ocular alkali burns. Am J Pathol. 2017; 187: 1327\u20131342.","DOI":"10.1016\/j.ajpath.2017.02.005"},{"key":"i2164-2591-8-2-6-b29","unstructured":"Paranthan R, Bargagna-Mohan P, Lau DL, Mohan R. A robust model for simultaneously inducing corneal neovascularization and retinal gliosis in the mouse eye. Mol Vis. 2011; 17: 1901\u20131908."},{"key":"i2164-2591-8-2-6-b30","unstructured":"Wizeman JW, Nicholas AP, Ishigami A., Mohan R. Citrullination of glial intermediate filaments is an early response in retinal injury. Mol Vis. 2016; 22: 1137\u20131155."},{"key":"i2164-2591-8-2-6-b31","doi-asserted-by":"crossref","unstructured":"Wizeman JW, Mohan R. Expression of peptidylarginine deiminase 4 in an alkali injury model of retinal gliosis. Biochem Biophys Res Commun 2017; 487: 134\u2013139.","DOI":"10.1016\/j.bbrc.2017.04.031"},{"key":"i2164-2591-8-2-6-b32","doi-asserted-by":"crossref","unstructured":"Xiang Y, Zhou W, Wang P, et al. Alkali burn induced corneal spontaneous pain and activated neuropathic pain matrix in the central nervous system in mice. Cornea. 2017; 36: 1408\u20131414.","DOI":"10.1097\/ICO.0000000000001336"},{"key":"i2164-2591-8-2-6-b33","doi-asserted-by":"crossref","unstructured":"Farazifard R, Safarpour F, Sheibani V, Javan M. Eye-wiping test: a sensitive animal model for acute trigeminal pain studies. Brain Res Brain Res Protoc. 2005; 16: 44\u201349.","DOI":"10.1016\/j.brainresprot.2005.10.003"},{"key":"i2164-2591-8-2-6-b34","doi-asserted-by":"crossref","unstructured":"Patel DV, McGhee CN. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol. 2009; 93: 853\u2013860.","DOI":"10.1136\/bjo.2008.150615"},{"key":"i2164-2591-8-2-6-b35","doi-asserted-by":"crossref","unstructured":"Cruzat A, Qazi Y, Hamrah P. In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf. 2017; 15: 15\u201347.","DOI":"10.1016\/j.jtos.2016.09.004"},{"key":"i2164-2591-8-2-6-b36","doi-asserted-by":"crossref","unstructured":"Aggarwal S, Kheirkhah A, Cavalcanti BM et al. Autologous serum tears for treatment of photoallodynia in patients with corneal neuropathy: efficacy and evaluation with in vivo confocal microscopy. Ocul Surf. 2015; 13: 250\u2013262.","DOI":"10.1016\/j.jtos.2015.01.005"},{"key":"i2164-2591-8-2-6-b37","doi-asserted-by":"crossref","unstructured":"De Cilla S, Ranno S, Carini E, et al. Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study. Invest Ophthalmol Vis. Sci. 2009; 50: 5155\u20135158.","DOI":"10.1167\/iovs.09-3384"},{"key":"i2164-2591-8-2-6-b38","doi-asserted-by":"crossref","unstructured":"Zhivov A, Winter K, Hovakimyan M, et al. Imaging and quantification of subbasal nerve plexus in healthy volunteers and diabetic patients with or without retinopathy. PLoS One. 2013; 8: e52157.","DOI":"10.1371\/journal.pone.0052157"},{"key":"i2164-2591-8-2-6-b39","doi-asserted-by":"crossref","unstructured":"Shetty R, Deshpande K, Deshmukh R, Jayadev C, Shroff R. Bowman break and subbasal nerve plexus changes in a patient with dry eye presenting with chronic ocular pain and vitamin D deficiency. Cornea. 35: 688\u2013691.","DOI":"10.1097\/ICO.0000000000000785"},{"key":"i2164-2591-8-2-6-b40","doi-asserted-by":"crossref","unstructured":"Tashiro A, Okamoto K, Chang Z, Bereiter DA. Behavioral and neurophysiological correlates of nociception in an animal model of photokeratitis. Neuroscience. 2010; 169: 455\u2013462.","DOI":"10.1016\/j.neuroscience.2010.04.034"},{"key":"i2164-2591-8-2-6-b41","doi-asserted-by":"crossref","unstructured":"Acosta MC, Luna C, Quirce S, Belmonte C, Gallar J. Corneal sensory nerve activity in an experimental model of UV keratitis. Invest Ophthalmol Vis. Sci. 2014; 55: 3403\u20133412.","DOI":"10.1167\/iovs.13-13774"},{"key":"i2164-2591-8-2-6-b42","doi-asserted-by":"crossref","unstructured":"Launay PS, Reboussin E, Liang H, et al. Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms. Neurobiol Dis 2016; 88: 16\u201328.","DOI":"10.1016\/j.nbd.2015.12.017"},{"key":"i2164-2591-8-2-6-b43","doi-asserted-by":"crossref","unstructured":"Ji RR, Baba H, Brenner GJ, Woolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci. 1999; 2: 1114\u20131119.","DOI":"10.1038\/16040"},{"key":"i2164-2591-8-2-6-b44","doi-asserted-by":"crossref","unstructured":"Gao YJ, Ji RR. c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury? Open Pain J. 2009; 2: 11\u201317.","DOI":"10.2174\/1876386300902010011"},{"key":"i2164-2591-8-2-6-b45","doi-asserted-by":"crossref","unstructured":"Cady RJ, Glenn JR, Smith KM, Durham PL. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization. Mol Pain. 2011; 7: 94.","DOI":"10.1186\/1744-8069-7-94"},{"key":"i2164-2591-8-2-6-b46","doi-asserted-by":"crossref","unstructured":"Csati A, Edvinsson L, Vecsei L, et al. Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion. J Headache Pain. 2015; 16: 99.","DOI":"10.1186\/s10194-015-0581-x"},{"key":"i2164-2591-8-2-6-b47","doi-asserted-by":"crossref","unstructured":"Zhang Q, Cao DL, Zhang ZJ, Jiang BC, Gao YJ. Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5\/ERK pathway in the trigeminal ganglion of mice. J Neuroinflammation. 2016; 13: 183.","DOI":"10.1186\/s12974-016-0652-1"},{"key":"i2164-2591-8-2-6-b48","doi-asserted-by":"crossref","unstructured":"Toyama M, Kudo C, Mukai C, et al. Trigeminal nervous system sensitization by infraorbital nerve injury enhances responses in a migraine model. Cephalalgia 2017; 37: 1317\u20131328.","DOI":"10.1177\/0333102416678387"},{"key":"i2164-2591-8-2-6-b49","doi-asserted-by":"crossref","unstructured":"Belmonte C, Acosta MC, Merayo-Lloves J, Gallar J. What causes eye pain? Curr Ophthalmol Rep. 2015; 3: 111\u2013121.","DOI":"10.1007\/s40135-015-0073-9"},{"key":"i2164-2591-8-2-6-b50","doi-asserted-by":"crossref","unstructured":"Galor A, Levitt RC, Felix ER, Martin ER, Sarantopoulos CD. Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond). 2015; 29: 301\u2013312.","DOI":"10.1038\/eye.2014.263"},{"key":"i2164-2591-8-2-6-b51","doi-asserted-by":"crossref","unstructured":"Galor A, Covington D, Levitt AE, et al. Neuropathic ocular pain due to dry eye is associated with multiple comorbid chronic pain syndromes. J Pain. 2016; 17: 310\u2013318.","DOI":"10.1016\/j.jpain.2015.10.019"},{"key":"i2164-2591-8-2-6-b52","doi-asserted-by":"crossref","unstructured":"Hamrah P, Qazi Y, Shahatit B, et al. Corneal nerve and epithelial cell alterations in corneal allodynia: an in vivo confocal microscopy case series. Ocul Surf. 2017; 15: 139\u2013151.","DOI":"10.1016\/j.jtos.2016.10.002"}],"container-title":["Translational Vision Science &amp; Technology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/tvst.arvojournals.org\/article.aspx?articleid=2729565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T03:48:56Z","timestamp":1574394536000},"score":1,"resource":{"primary":{"URL":"http:\/\/tvst.arvojournals.org\/article.aspx?doi=10.1167\/tvst.8.2.6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,26]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1167\/tvst.8.2.6","relation":{},"ISSN":["2164-2591"],"issn-type":[{"value":"2164-2591","type":"print"}],"subject":[],"published":{"date-parts":[[2019,3,26]]}}}