Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease

Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in th...

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Autores principales: Kovács, Illés, Luna, Carolina, Quirce, Susana, Mizerska, Kamila, Callejo, Gerard, Riestra, Ana, Fernández-Sánchez, Laura, Meseguer, Victor M., Cuenca, Nicolás, Merayo-Lloves, Jesús, Acosta, M. Carmen, Gasull, Xavier, Belmonte, Carlos, Gallar, Juana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733818/
https://www.ncbi.nlm.nih.gov/pubmed/26675826
http://dx.doi.org/10.1097/j.pain.0000000000000455
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author Kovács, Illés
Luna, Carolina
Quirce, Susana
Mizerska, Kamila
Callejo, Gerard
Riestra, Ana
Fernández-Sánchez, Laura
Meseguer, Victor M.
Cuenca, Nicolás
Merayo-Lloves, Jesús
Acosta, M. Carmen
Gasull, Xavier
Belmonte, Carlos
Gallar, Juana
author_facet Kovács, Illés
Luna, Carolina
Quirce, Susana
Mizerska, Kamila
Callejo, Gerard
Riestra, Ana
Fernández-Sánchez, Laura
Meseguer, Victor M.
Cuenca, Nicolás
Merayo-Lloves, Jesús
Acosta, M. Carmen
Gasull, Xavier
Belmonte, Carlos
Gallar, Juana
author_sort Kovács, Illés
collection PubMed
description Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.
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spelling pubmed-47338182016-02-10 Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease Kovács, Illés Luna, Carolina Quirce, Susana Mizerska, Kamila Callejo, Gerard Riestra, Ana Fernández-Sánchez, Laura Meseguer, Victor M. Cuenca, Nicolás Merayo-Lloves, Jesús Acosta, M. Carmen Gasull, Xavier Belmonte, Carlos Gallar, Juana Pain Research Paper Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 μM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED. Wolters Kluwer 2015-12-15 2016-02 /pmc/articles/PMC4733818/ /pubmed/26675826 http://dx.doi.org/10.1097/j.pain.0000000000000455 Text en © 2015 International Association for the Study of Pain
spellingShingle Research Paper
Kovács, Illés
Luna, Carolina
Quirce, Susana
Mizerska, Kamila
Callejo, Gerard
Riestra, Ana
Fernández-Sánchez, Laura
Meseguer, Victor M.
Cuenca, Nicolás
Merayo-Lloves, Jesús
Acosta, M. Carmen
Gasull, Xavier
Belmonte, Carlos
Gallar, Juana
Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title_full Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title_fullStr Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title_full_unstemmed Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title_short Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
title_sort abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733818/
https://www.ncbi.nlm.nih.gov/pubmed/26675826
http://dx.doi.org/10.1097/j.pain.0000000000000455
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