A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model
IntroductionNeuropathic pain arises as a result of peripheral nerve injury or altered pain processing within the central nervous system. When this phenomenon affects the cornea, it is referred to as neuropathic corneal pain (NCP), resulting in pain, hyperalgesia, burning, and photoallodynia, severel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1265708/full |
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| author | Yashar Seyed-Razavi Yashar Seyed-Razavi Brendan M. Kenyon Brendan M. Kenyon Brendan M. Kenyon Fangfang Qiu Fangfang Qiu Deshea L. Harris Deshea L. Harris Pedram Hamrah Pedram Hamrah Pedram Hamrah Pedram Hamrah |
| author_facet | Yashar Seyed-Razavi Yashar Seyed-Razavi Brendan M. Kenyon Brendan M. Kenyon Brendan M. Kenyon Fangfang Qiu Fangfang Qiu Deshea L. Harris Deshea L. Harris Pedram Hamrah Pedram Hamrah Pedram Hamrah Pedram Hamrah |
| author_sort | Yashar Seyed-Razavi |
| collection | DOAJ |
| description | IntroductionNeuropathic pain arises as a result of peripheral nerve injury or altered pain processing within the central nervous system. When this phenomenon affects the cornea, it is referred to as neuropathic corneal pain (NCP), resulting in pain, hyperalgesia, burning, and photoallodynia, severely affecting patients’ quality of life. To date there is no suitable animal model for the study of NCP. Herein, we developed an NCP model by constriction of the long ciliary nerves innervating the eye.MethodsMice underwent ciliary nerve constriction (CNC) or sham procedures. Safety was determined by corneal fluorescein staining to assess ocular surface damage, whereas Cochet-Bonnet esthesiometry and confocal microscopy assessed the function and structure of corneal nerves, respectively. Efficacy was assessed by paw wipe responses within 30 seconds of applying hyperosmolar (5M) saline at Days 3, 7, 10, and 14 post-constriction. Additionally, behavior was assessed in an open field test (OFT) at Days 7, 14, and 21.ResultsCNC resulted in significantly increased response to hyperosmolar saline between groups (p < 0.0001), demonstrating hyperalgesia and induction of neuropathic pain. Further, animals that underwent CNC had increased anxiety-like behavior in an open field test compared to controls at the 14- and 21-Day time-points (p < 0.05). In contrast, CNC did not result in increased corneal fluorescein staining or decreased sensation as compared to sham controls (p > 0.05). Additionally, confocal microscopy of corneal whole-mounts revealed that constriction resulted in only a slight reduction in corneal nerve density (p < 0.05), compared to naïve and sham groups.DiscussionThe CNC model induces a pure NCP phenotype and may be a useful model for the study of NCP, recapitulating features of NCP, including hyperalgesia in the absence of ocular surface damage, and anxiety-like behavior. |
| first_indexed | 2024-03-09T01:59:13Z |
| format | Article |
| id | doaj.art-efe5ca6c1b07437eb62e4c5eb52e8b69 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-09T01:59:13Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-efe5ca6c1b07437eb62e4c5eb52e8b692023-12-08T11:02:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-12-011710.3389/fnins.2023.12657081265708A novel animal model of neuropathic corneal pain–the ciliary nerve constriction modelYashar Seyed-Razavi0Yashar Seyed-Razavi1Brendan M. Kenyon2Brendan M. Kenyon3Brendan M. Kenyon4Fangfang Qiu5Fangfang Qiu6Deshea L. Harris7Deshea L. Harris8Pedram Hamrah9Pedram Hamrah10Pedram Hamrah11Pedram Hamrah12Center for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United StatesDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United StatesCenter for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United StatesDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United StatesProgram in Neuroscience, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United StatesCenter for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United StatesDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United StatesCenter for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United StatesDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United StatesCenter for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United StatesDepartment of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United StatesProgram in Neuroscience, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United StatesDepartments of Neuroscience and Immunology, Tufts University School of Medicine, Boston, MA, United StatesIntroductionNeuropathic pain arises as a result of peripheral nerve injury or altered pain processing within the central nervous system. When this phenomenon affects the cornea, it is referred to as neuropathic corneal pain (NCP), resulting in pain, hyperalgesia, burning, and photoallodynia, severely affecting patients’ quality of life. To date there is no suitable animal model for the study of NCP. Herein, we developed an NCP model by constriction of the long ciliary nerves innervating the eye.MethodsMice underwent ciliary nerve constriction (CNC) or sham procedures. Safety was determined by corneal fluorescein staining to assess ocular surface damage, whereas Cochet-Bonnet esthesiometry and confocal microscopy assessed the function and structure of corneal nerves, respectively. Efficacy was assessed by paw wipe responses within 30 seconds of applying hyperosmolar (5M) saline at Days 3, 7, 10, and 14 post-constriction. Additionally, behavior was assessed in an open field test (OFT) at Days 7, 14, and 21.ResultsCNC resulted in significantly increased response to hyperosmolar saline between groups (p < 0.0001), demonstrating hyperalgesia and induction of neuropathic pain. Further, animals that underwent CNC had increased anxiety-like behavior in an open field test compared to controls at the 14- and 21-Day time-points (p < 0.05). In contrast, CNC did not result in increased corneal fluorescein staining or decreased sensation as compared to sham controls (p > 0.05). Additionally, confocal microscopy of corneal whole-mounts revealed that constriction resulted in only a slight reduction in corneal nerve density (p < 0.05), compared to naïve and sham groups.DiscussionThe CNC model induces a pure NCP phenotype and may be a useful model for the study of NCP, recapitulating features of NCP, including hyperalgesia in the absence of ocular surface damage, and anxiety-like behavior.https://www.frontiersin.org/articles/10.3389/fnins.2023.1265708/fullneuropathic corneal painocular painnociceptionchronic constriction injuryanimal model |
| spellingShingle | Yashar Seyed-Razavi Yashar Seyed-Razavi Brendan M. Kenyon Brendan M. Kenyon Brendan M. Kenyon Fangfang Qiu Fangfang Qiu Deshea L. Harris Deshea L. Harris Pedram Hamrah Pedram Hamrah Pedram Hamrah Pedram Hamrah A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model Frontiers in Neuroscience neuropathic corneal pain ocular pain nociception chronic constriction injury animal model |
| title | A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model |
| title_full | A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model |
| title_fullStr | A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model |
| title_full_unstemmed | A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model |
| title_short | A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model |
| title_sort | novel animal model of neuropathic corneal pain the ciliary nerve constriction model |
| topic | neuropathic corneal pain ocular pain nociception chronic constriction injury animal model |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1265708/full |
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