Evidence map›Paper›PMID 39839966›Full record

ArticlePain reports2025

Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease.

Amirreza Naderi, Yukako Taketani, Shudan Wang, Francesca Kahale, Ann Yung, Pier Luigi Surico, Yihe Chen, Reza Dana

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pain reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Observational
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Amirreza NaderiDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Yukako TaketaniDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Shudan WangDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Francesca KahaleDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Ann YungDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Pier Luigi SuricoDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.
Yihe ChenDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.ORCID https://orcid.org/0000-0002-2336-6182
Reza DanaDepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USA.

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
Immunopathogenic Mechanisms of Dry Eye DiseaseR01EY020889 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Reza Dana · 2010 to 2026
$7.9M
NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY020889
6 · The paper itself

Abstract

Introduction: Ocular pain is a common complaint to eye care providers, associated with a variety of ocular conditions, among which dry eye disease (DED) is affecting millions of people worldwide. Despite being highly prevalent, ocular pain is not managed adequately in the clinic. Objectives: The aim of this study was to investigate the analgesic potential of neurokinin-1 receptor (NK1R) antagonism in DED. Methods: Dry eye disease was induced in mice, and an NK1R antagonist L-733,060 was topically administered twice daily throughout the study for 14 days. Hyperalgesia and allodynia were assessed using the eye-wiping test and palpebral ratio measurements. Corneas were collected for measuring substance P (SP) levels by enzyme-linked immunosorbent assay (ELISA) and imaging nerves by immunostaining. Trigeminal ganglions (TG) were collected to determine SP levels by ELISA and transient receptor potential cation channel subfamily V member 1 (TRPV1), transient receptor potential cation channel subfamily M (melastatin) member 8, c-Fos, and activating transcription factor 3 (ATF3) mRNA levels by real-time polymerase chain reaction. Results: Treating DED mice with L-733,060 resulted in a significant reduction in eye wipe behavior, a significant increase in palpebral ratio, and significant decreases in SP levels in both the cornea and TG compared with the vehicle-treated group. In addition, NK1R antagonist treatment significantly suppressed the upregulation of TRPV1, ATF3, and c-Fos and prevented corneal nerve loss. Conclusion: Neurokinin-1 receptor antagonism effectively reduced ocular nociception, decreased neuronal activation, and preserved corneal nerves in mice with DED. These findings suggest that blockade of SP signaling pathway is a promising therapeutic strategy for managing DED pain.

Indexed as

Dry eye diseaseEye-wiping testNeurokinin-1 receptorPalpebral ratioSubstance PTrigeminal ganglion

Identifiers

PMID39839966
PMCPMC11745868

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.