| First Author | Li F | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5678 |
| PubMed ID | 31831729 | Mgi Jnum | J:286813 |
| Mgi Id | MGI:6388350 | Doi | 10.1038/s41467-019-13536-0 |
| Citation | Li F, et al. (2019) TRPV1 activity and substance P release are required for corneal cold nociception. Nat Commun 10(1):5678 |
| abstractText | 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. |
