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Targeting ion channels to treat corneal neuropathic pain and dry eye
Author(s) -
Gallar Juana
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8032
Subject(s) - neuropathic pain , trpm8 , ion channel , neuroscience , stimulus (psychology) , chemistry , trpv1 , sensory system , transduction (biophysics) , free nerve ending , trigeminal ganglion , nociceptor , transient receptor potential channel , biophysics , medicine , anatomy , nociception , psychology , biology , receptor , biochemistry , psychotherapist
Ocular sensations and pain results from the activation of peripheral nerve endings of trigeminal ganglion neurons whose sensitivity to different types of stimulus depends on the expression in their membrane of specific ion channels involved in sensory transduction. TRPM8 channel provides sensitivity to temperature changes and osmolarity; TRPV1, TRPA1 and ASIC channels, to chemical and heat stimuli, and Piezo2 channels, to mechanical forces. Other ion channels present in nerve endings as Ca v , Na v , K v , HCN and (2PD)K + modulate their excitability and contribute to encode the stimulus. After nerve injury, sensory nerves firing is altered due to changes in the expression/activity of both transducing and excitability‐modulating ion channels, being this altered activity the basis of neuropathic pain. Then, transducing and encoding ion channels are potential molecular targets to modulate neuropathic nerve activity. Besides the classical use of drugs modulating the activity of TRPM8, TRPV1, Ca 2+ , Na + or Kv channels, new approaches like the use of small molecule photoswitches (optopharmacology) are promising tools to alternatively block and unblock those ion channels involved in corneal neuropathic pain and dry eye. (Supported by grants SAF‐2017‐83674‐C2‐2‐R and 1‐R from Agencia Estatal de Investigación, Spain, and ERDF, EU, and PROMETEO/2018/114 from Generalitat Valenciana, Spain).