title: Ocular dryness excites two classes of corneal afferent neurons implicated in basal tearing in rats: involvement of transient receptor potential channels.
abstract: This study reports the findings of two classes of corneal afferents excited by drying of the cornea (dry responses) in isoflurane-anesthetized rats: cold-sensitive (CS; 87%) and cold-insensitive (CI; 13%) neurons. Compared with CI neurons, CS neurons showed significantly higher firing rates over warmer corneal temperatures (~31-15°C) and greater responses to menthol, drying, and wetting of the cornea but lower responses when hyperosmolar solutions were applied to the ocular surface. We proposed that the dry responses of these corneal afferents derive from cooling and an increased osmolarity of the ocular surface, leading to the production of basal tears. An ocular application of the transient receptor potential channel TRPM8 antagonist BCTC (20 μM) decreased the dry responses by ~45-80% but failed to completely block them, whereas the TRPA1 antagonist HC030031 did not influence the responses to drying of the cornea or hyperosmolar tears. Furthermore, the responses produced by cold stimulation of the cornea accounted for only 28% of the dry responses. These results support the view that the stimulus for basal tearing (corneal dryness) derives partly from cooling of the cornea that activates TRPM8 channels but that non-TRPM8 channels also contribute significantly to the dry responses and to basal tearing. Finally, we hypothesized that activation of TRPM8 by cooling in CS corneal afferents not only gives rise to the sensation of ocular coolness but also to the "wetness" perception (Thunberg's illusion), whereas a precise role of the CI afferents in basal tearing and other ocular dryness-related functions such as eye blink and the "dryness" sensation remain to be elucidated.
authors: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. harumitsu.hirata@jefferson.edu
authors: Harumitsu
authors: H
authors: Hirata
authors: Michael L
authors: ML
authors: Oshinsky
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D003315:Cornea / Q000294:innervation*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000209:etiology / Q000473:pathology*; D005123:Eye / Q000033:anatomy & histology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D011687:Purines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013268:Stimulation, Chemical; D013666:Tears; D013696:Temperature; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011687:Purines; D011719:Pyrazines; D011725:Pyridines; D050051:Transient Receptor Potential Channels; D008353:Mannitol