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- Title
TRPV1 activity and substance P release are required for corneal cold nociception.
- Authors
Li, Fengxian; Yang, Weishan; Jiang, Haowu; Guo, Changxiong; Huang, Andrew J. W.; Hu, Hongzhen; Liu, Qin
- Abstract
As a protective mechanism, the cornea is sensitive to noxious stimuli. Here, we show that in mice, a high proportion of corneal TRPM8+ cold-sensing fibers express the heat-sensitive TRPV1 channel. Despite its insensitivity to cold, TRPV1 enhances membrane potential changes and electrical firing of TRPM8+ neurons in response to cold stimulation. This elevated neuronal excitability leads to augmented ocular cold nociception in mice. In a model of dry eye disease, the expression of TRPV1 in TRPM8+ cold-sensing fibers is increased, and results in severe cold allodynia. Overexpression of TRPV1 in TRPM8+ sensory neurons leads to cold allodynia in both corneal and non-corneal tissues without affecting their thermal sensitivity. TRPV1-dependent neuronal sensitization facilitates the release of the neuropeptide substance P from TRPM8+ cold-sensing neurons to signal nociception in response to cold. Our study identifies a mechanism underlying corneal cold nociception and suggests a potential target for the treatment of ocular pain. The eye shows protective responses to noxious stimuli including cold. Here, the authors show that TRPV1, found co-expressed on TRPM8 + fibres in the cornea, is necessary for cold nociception in the eye.
- Subjects
EYE diseases; TRPV cation channels; SUBSTANCE P; MEMBRANE potential; AVERSIVE stimuli
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-13536-0