TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization Article Swipe
Roberta Gualdani
,
Solène Barbeau
,
Jun‐Hui Yuan
,
Deborah S. Jacobs
,
Philippe Gailly
,
Sulayman D. Dib‐Hajj
,
Stephen G. Waxman
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2406186121
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2406186121
The factors that contribute to pain after nerve injury remain incompletely understood. Laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) are common surgical techniques to correct refractive errors. After LASIK or PRK, a subset of patients suffers intense and persistent pain, of unknown origin, described by patients as feeling like shards of glass in their eye. Here, we evaluated a TRPV1 variant, p.V527M, found in a 49-y-old woman who developed corneal pain after LASIK and subsequent PRK enhancement, reporting an Ocular Surface Disease Index score of 100. Using patch-clamp and Ca 2+ imaging, we found that the V527M mutation enhances the response to acidic pH. Increasing proton concentration induced a stronger leftward shift in the activation curve of V527M compared to WT, resulting in channel activity of the mutant in acidic pH at more physiological membrane potentials. Finally, comparing the responses to consecutive applications of different agonists, we found in V527M channels a reduced capsaicin-induced desensitization and increased sensitization by the arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE). We hypothesize that the increased response in V527M channels to protons and enhanced sensitization by 12-HETE, two inflammatory mediators released in the cornea after tissue damage, may contribute to the pathogenesis of corneal neuralgia after refractive surgery.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2406186121
- OA Status
- green
- Cited By
- 7
- References
- 83
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402208482
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4402208482Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1073/pnas.2406186121Digital Object Identifier
- Title
-
TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitizationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-09-03Full publication date if available
- Authors
-
Roberta Gualdani, Solène Barbeau, Jun‐Hui Yuan, Deborah S. Jacobs, Philippe Gailly, Sulayman D. Dib‐Hajj, Stephen G. WaxmanList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2406186121Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://hdl.handle.net/2078.1/291520Direct OA link when available
- Concepts
-
Sensitization, Capsaicin, Cornea, LASIK, TRPV1, Ophthalmology, Medicine, Photorefractive keratectomy, Pathogenesis, Keratomileusis, Chemistry, Anesthesia, Internal medicine, Immunology, Transient receptor potential channel, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 3Per-year citation counts (last 5 years)
- References (count)
-
83Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.woman | 68 |
| abstract_inverted_index.Ocular | 81 |
| abstract_inverted_index.acidic | 104, 131 |
| abstract_inverted_index.common | 22 |
| abstract_inverted_index.cornea | 190 |
| abstract_inverted_index.injury | 8 |
| abstract_inverted_index.mutant | 129 |
| abstract_inverted_index.proton | 107 |
| abstract_inverted_index.remain | 9 |
| abstract_inverted_index.shards | 51 |
| abstract_inverted_index.subset | 34 |
| abstract_inverted_index.tissue | 192 |
| abstract_inverted_index.(LASIK) | 16 |
| abstract_inverted_index.Disease | 83 |
| abstract_inverted_index.Surface | 82 |
| abstract_inverted_index.channel | 125 |
| abstract_inverted_index.corneal | 71, 200 |
| abstract_inverted_index.correct | 26 |
| abstract_inverted_index.damage, | 193 |
| abstract_inverted_index.errors. | 28 |
| abstract_inverted_index.factors | 1 |
| abstract_inverted_index.feeling | 49 |
| abstract_inverted_index.induced | 109 |
| abstract_inverted_index.intense | 38 |
| abstract_inverted_index.origin, | 44 |
| abstract_inverted_index.protons | 178 |
| abstract_inverted_index.reduced | 154 |
| abstract_inverted_index.suffers | 37 |
| abstract_inverted_index.unknown | 43 |
| abstract_inverted_index.12-HETE, | 183 |
| abstract_inverted_index.49-y-old | 67 |
| abstract_inverted_index.Finally, | 138 |
| abstract_inverted_index.activity | 126 |
| abstract_inverted_index.channels | 152, 176 |
| abstract_inverted_index.compared | 120 |
| abstract_inverted_index.enhanced | 180 |
| abstract_inverted_index.enhances | 100 |
| abstract_inverted_index.imaging, | 93 |
| abstract_inverted_index.leftward | 112 |
| abstract_inverted_index.membrane | 136 |
| abstract_inverted_index.mutation | 99 |
| abstract_inverted_index.p.V527M, | 63 |
| abstract_inverted_index.patients | 36, 47 |
| abstract_inverted_index.released | 187 |
| abstract_inverted_index.response | 102, 173 |
| abstract_inverted_index.stronger | 111 |
| abstract_inverted_index.surgery. | 204 |
| abstract_inverted_index.surgical | 23 |
| abstract_inverted_index.variant, | 62 |
| abstract_inverted_index.agonists, | 147 |
| abstract_inverted_index.comparing | 139 |
| abstract_inverted_index.described | 45 |
| abstract_inverted_index.developed | 70 |
| abstract_inverted_index.different | 146 |
| abstract_inverted_index.evaluated | 59 |
| abstract_inverted_index.increased | 158, 172 |
| abstract_inverted_index.mediators | 186 |
| abstract_inverted_index.neuralgia | 201 |
| abstract_inverted_index.reporting | 79 |
| abstract_inverted_index.responses | 141 |
| abstract_inverted_index.resulting | 123 |
| abstract_inverted_index.(12-HETE). | 167 |
| abstract_inverted_index.Increasing | 106 |
| abstract_inverted_index.activation | 116 |
| abstract_inverted_index.contribute | 3, 195 |
| abstract_inverted_index.metabolite | 164 |
| abstract_inverted_index.persistent | 40 |
| abstract_inverted_index.refractive | 27, 203 |
| abstract_inverted_index.subsequent | 76 |
| abstract_inverted_index.techniques | 24 |
| abstract_inverted_index.arachidonic | 162 |
| abstract_inverted_index.consecutive | 143 |
| abstract_inverted_index.hypothesize | 169 |
| abstract_inverted_index.keratectomy | 19 |
| abstract_inverted_index.patch-clamp | 89 |
| abstract_inverted_index.potentials. | 137 |
| abstract_inverted_index.understood. | 11 |
| abstract_inverted_index.applications | 144 |
| abstract_inverted_index.enhancement, | 78 |
| abstract_inverted_index.incompletely | 10 |
| abstract_inverted_index.inflammatory | 185 |
| abstract_inverted_index.pathogenesis | 198 |
| abstract_inverted_index.concentration | 108 |
| abstract_inverted_index.physiological | 135 |
| abstract_inverted_index.sensitization | 159, 181 |
| abstract_inverted_index.Laser-assisted | 12 |
| abstract_inverted_index.keratomileusis | 15 |
| abstract_inverted_index.desensitization | 156 |
| abstract_inverted_index.photorefractive | 18 |
| abstract_inverted_index.capsaicin-induced | 155 |
| abstract_inverted_index.12-hydroxyeicosatetraenoic | 165 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 96 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 7 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7699999809265137 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.95622957 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |