Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease
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. Objectiv...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2025-02-01
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| Series: | PAIN Reports |
| Online Access: | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001232 |
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| author | Amirreza Naderi Yukako Taketani Shudan Wang Francesca Kahale Ann Yung Pier Luigi Surico Yihe Chen Reza Dana |
| author_facet | Amirreza Naderi Yukako Taketani Shudan Wang Francesca Kahale Ann Yung Pier Luigi Surico Yihe Chen Reza Dana |
| author_sort | Amirreza Naderi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0b52535f226445078e9486df3cd4010f |
| institution | Kabale University |
| issn | 2471-2531 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | PAIN Reports |
| spelling | doaj-art-0b52535f226445078e9486df3cd4010f2025-01-24T09:20:44ZengWolters KluwerPAIN Reports2471-25312025-02-01101e123210.1097/PR9.0000000000001232PR90000000000001232Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye diseaseAmirreza Naderi0Yukako Taketani1Shudan Wang2Francesca Kahale3Ann Yung4Pier Luigi Surico5Yihe Chen6Reza Dana7Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USADepartment of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, MA, USAAbstract. 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.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001232 |
| spellingShingle | Amirreza Naderi Yukako Taketani Shudan Wang Francesca Kahale Ann Yung Pier Luigi Surico Yihe Chen Reza Dana Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease PAIN Reports |
| title | Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| title_full | Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| title_fullStr | Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| title_full_unstemmed | Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| title_short | Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| title_sort | topical neurokinin 1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease |
| url | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001232 |
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