ArticleInvestigative ophthalmology & visual science2014
Hyperosmolar tears enhance cooling sensitivity of the corneal nerves in rats: possible neural basis for cold-induced dry eye pain.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Article
- Multidimensional immunotherapy for dry eye disease: current status and future directions.Frontiers in ophthalmology · 2024Review
- Impact of Clinician Subjectivity on the Assessment of Dry Eye Disease Prevalence in a UK Public Health Care Patient Population.Clinical ophthalmology (Auckland, N.Z.) · 2024Article
- Benzalkonium chloride, a common ophthalmic preservative, compromises rat corneal cold sensitive nerve activity.The ocular surface · 2022Article
- Corneal nerves and their role in dry eye pathophysiology.Experimental eye research · 2022Review
- The Role of Neuropeptides in Pathogenesis of Dry Dye.Journal of clinical medicine · 2021Review
- Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain.Frontiers in pharmacology · 2021Review
- Changes in Corneal Detection Thresholds After Repeated Tear Film Instability.Investigative ophthalmology & visual science · 2019Article
- Corneal pain and experimental model development.Progress in retinal and eye research · 2019Review
- Effects of Tear Film Instability on Sensory Responses to Corneal Cold, Mechanical, and Chemical Stimuli.Investigative ophthalmology & visual science · 2019Article
- Ambient Air Currents Activate Corneal Nerves During Ocular Desiccation in Rats: Simultaneous Recordings of Neural Activity and Corneal Temperature.Investigative ophthalmology & visual science · 2018Article
- Mechanisms, imaging and structure of tear film breakup.The ocular surface · 2018Review
- TFOS DEWS II pain and sensation report.The ocular surface · 2017Review
- Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye.Journal of neurophysiology · 2017Article
- Estimating the Osmolarities of Tears During Evaporation Through the "Eyes" of the Corneal Nerves.Investigative ophthalmology & visual science · 2017Article
- In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease.The ocular surface · 2017Review
- Hypersensitivity to Cold Stimuli in Symptomatic Contact Lens Wearers.Optometry and vision science : official publication of the American Academy of Optometry · 2016Article
- Article
- Ocular neuropathic pain.The British journal of ophthalmology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTear hyperosmolarity is a ubiquitous feature of dry-eye disease. Although dry-eye patients' sensitivity to cooling is well known, the effects of tear hyperosmolarity on a small amount of cooling in the corneal nerves have not been quantitatively examined. Recently reported corneal afferents, high-threshold cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally excited by strong (>4°C) cooling of the cornea, which, when applied to healthy humans, evokes the sensation of discomfort. However, corneal cooling measured between blinks does not exceed 2°C normally. Thus, we sought to determine if these nociceptors could be sensitized by hyperosmolar tears such that they are now activated by small cooling of the ocular surface.
methodsTrigeminal ganglion neurons innervating the cornea were extracellularly recorded in isoflurane-anesthetized rats. The responses of single corneal neurons to cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl) tears were examined.
resultsThe HT-CS + DS neurons with thresholds averaging 4°C cooling responded to cooling stimuli presented after 15 minutes of hyperosmolar tears with thresholds of less than 1°C. The response magnitudes also were enhanced so that the responses to small (2°C) cooling emerged, where none was observed before.
conclusionsThese results demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal neurons now begin to respond to the slight cooling normally encountered between blinks, enabling the painful information to be carried to the brain, which could explain the cooling-evoked discomfort in dry eye patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.