A novel animal model of neuropathic corneal pain-the ciliary nerve constriction model

Yashar Seyed-Razavi; Brendan M Kenyon; Fangfang Qiu; Deshea L Harris; Pedram Hamrah

doi:10.3389/fnins.2023.1265708

A novel animal model of neuropathic corneal pain-the ciliary nerve constriction model

Front Neurosci. 2023 Dec 8:17:1265708. doi: 10.3389/fnins.2023.1265708. eCollection 2023.

Authors

Yashar Seyed-Razavi^#^{1

2}, Brendan M Kenyon^#^{1

2

3}, Fangfang Qiu^{1

2}, Deshea L Harris^{1

2}, Pedram Hamrah^{1

2

3

4}

Affiliations

¹ Center for Translational Ocular Immunology, Tufts Medical Center, Boston, MA, United States.
² Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United States.
³ Program in Neuroscience, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States.
⁴ Departments of Neuroscience and Immunology, Tufts University School of Medicine, Boston, MA, United States.

^# Contributed equally.

Abstract

Introduction: Neuropathic 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.

Methods: Mice 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.

Results: CNC 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.

Discussion: The 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.

Keywords: animal model; chronic constriction injury; neuropathic corneal pain; nociception; ocular pain.

Grants and funding

R01 EY029602/EY/NEI NIH HHS/United States