TRPV1 activity and substance P release are required for corneal cold nociception

Fengxian Li, Weishan Yang, Haowu Jiang, Changxiong Guo, Andrew J. W. Huang, Hongzhen Hu and Qin Liu ()
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Fengxian Li: Washington University School of Medicine
Weishan Yang: Washington University School of Medicine
Haowu Jiang: Washington University School of Medicine
Changxiong Guo: Washington University School of Medicine
Andrew J. W. Huang: Washington University School of Medicine
Hongzhen Hu: Washington University School of Medicine
Qin Liu: Washington University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13536-0

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