Cargando…
Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain
PURPOSE: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. METHODS: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in cornea...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606841/ https://www.ncbi.nlm.nih.gov/pubmed/34787642 http://dx.doi.org/10.1167/iovs.62.14.15 |
_version_ | 1784602422969106432 |
---|---|
author | Mecum, Neal E. Russell, Rachel Lee, Jun Sullivan, Cara Meng, Ian D. |
author_facet | Mecum, Neal E. Russell, Rachel Lee, Jun Sullivan, Cara Meng, Ian D. |
author_sort | Mecum, Neal E. |
collection | PubMed |
description | PURPOSE: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. METHODS: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. RESULTS: The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. CONCLUSIONS: Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain. |
format | Online Article Text |
id | pubmed-8606841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-86068412021-11-23 Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain Mecum, Neal E. Russell, Rachel Lee, Jun Sullivan, Cara Meng, Ian D. Invest Ophthalmol Vis Sci Cornea PURPOSE: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. METHODS: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. RESULTS: The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. CONCLUSIONS: Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain. The Association for Research in Vision and Ophthalmology 2021-11-17 /pmc/articles/PMC8606841/ /pubmed/34787642 http://dx.doi.org/10.1167/iovs.62.14.15 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. |
spellingShingle | Cornea Mecum, Neal E. Russell, Rachel Lee, Jun Sullivan, Cara Meng, Ian D. Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title | Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title_full | Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title_fullStr | Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title_full_unstemmed | Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title_short | Optogenetic Inhibition of Na(v)1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain |
title_sort | optogenetic inhibition of na(v)1.8 expressing corneal afferents reduces persistent dry eye pain |
topic | Cornea |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606841/ https://www.ncbi.nlm.nih.gov/pubmed/34787642 http://dx.doi.org/10.1167/iovs.62.14.15 |
work_keys_str_mv | AT mecumneale optogeneticinhibitionofnav18expressingcornealafferentsreducespersistentdryeyepain AT russellrachel optogeneticinhibitionofnav18expressingcornealafferentsreducespersistentdryeyepain AT leejun optogeneticinhibitionofnav18expressingcornealafferentsreducespersistentdryeyepain AT sullivancara optogeneticinhibitionofnav18expressingcornealafferentsreducespersistentdryeyepain AT mengiand optogeneticinhibitionofnav18expressingcornealafferentsreducespersistentdryeyepain |