Central and Peripheral Mechanisms of Corneal Pain

The Center of Biomedical Research Excellence (COBRE) for the Study of Pain and Sensory Function at the University of New England earned a five-year, NEI-funded project to map corneal nerves and investigate both central and peripheral mechanisms of corneal pain. Using $6.6 million from the National Eye Institute, this project aims to produce a comprehensive anatomical and functional characterization of the neurons that innervate the cornea and to trace how injury to those neurons alters neural circuits that mediate emotional and behavioral responses.

The cornea as the most densely innervated structure in the body, is uniquely positioned to signal potential threats to vision. Because vision is critical to daily function, corneal nerves are highly sensitive and can provoke intense pain responses even to minor stimuli. This project seeks to clarify why corneal pain is often accompanied by strong emotional reactions and why corneal pathology is frequently associated with other chronic pain conditions, such as headaches and migraines. The initial phase of the study focuses on an exhaustive mapping of corneal innervation, documenting nerve types, distribution, and connectivity. Subsequent phases will examine how acute injury and chronic conditions like dry eye disease alter peripheral nerve structure and function, and how those peripheral changes propagate to central nervous system targets.

Of particular interest is the pathway linking corneal sensory neurons to structures that feed into the limbic system — the brain network that governs emotion and behavioral responses. this team hypothesizes that corneal afferents have unusually direct or potent access to limbic circuits, which could explain the disproportionately strong affective responses observed in corneal pain and related comorbidities. Beyond fundamental discovery, the project emphasizes translational goals: understanding mechanisms that could guide the development of new, more effective treatments for corneal pain. By identifying which peripheral changes drive maladaptive central responses, the team aims to reveal targets for interventions that could limit both sensory and emotional suffering associated with corneal injury and chronic ocular surface disease. The NEI award supports a multi-principal-investigator consortium model in which several funded groups coordinate methods, share progress, and compare findings in a collaborative, transparent framework.

As part of this consortium, this group will both contribute to and learn from peer groups, enhancing reproducibility and the potential for rapid translation of discoveries into clinical strategies to alleviate corneal pain and its wider impacts.