A more robust conditioned pain modulation (CPM) response—a measure of descending (inhibitory) pain pathways—was associated with worse dry eye (DE) metrics, according to a study, suggesting that CPM is intact or even upregulated in DE.

“In our practice, we see patients who complain of DE symptoms, but upon further examination of the ocular surface, we are not able to find the source of their symptoms,” says study co-author Anat Galor, MD, MSPH, Staff Physician and Ophthalmologist at the Miami Veteran Affairs Medical Center, and Professor of Ophthalmology at the University of Miami. “However, the reverse is also true. Upon examining patients who do not complain of DE symptoms, we often find ocular abnormalities. We hypothesize that the missing piece of the puzzle that underlies these discrepancies are abnormalities in peripheral and central nerves that connect the cornea to the brain. Our overall research focuses on studying nerve function in individuals with painful DE symptoms to detect when nerve abnormalities contribute to symptoms.”


Findings Misaligned With Original Theory

For the study, Dr. Galor and colleagues specifically explored the connection between CPM responses and DE symptoms to examine if abnormalities in descending inhibitory pathways contribute to DE symptoms. The researchers conducted a cross-sectional study of 268 patients from October 2017 to August 2018. DE metrics were assessed via the Dry Eye Questionnaire (DEQ-5), numerical rating scales for eye pain intensity, and an ocular surface exam. CPM was assessed with a noxious (heat) stimulus, followed by a noxious conditioning (cold water bath) stimulus, and again followed by the original noxious stimulus at the forehead and forearm. Pain inhibition was considered a normal response.

The study team found a significant negative association between forehead CPM intensity ratings and DEQ5 responses (r = -0.22, P<.05). Forehead CPM intensity was also significantly associated with average eye pain intensity throughout 1 week (r = -0.18, P<.05). Similar findings were detected for forearm CPM unpleasantness ratings, which negatively correlated with eye pain (r = -0.26) and evoked pain severity due to light (r = -0.20), both <0.05. The findings indicate that individuals with more severe symptoms have a more robust CPM response, a finding opposite of what was originally theorized.

“Despite the unexpected findings, we concur that nerve dysfunction is a contributor to painful DE symptoms in some individuals and that we need better diagnostic tests to determine the presence and location of nerve abnormalities,” Dr. Galor says. “In this way, we can develop precision-based treatments for our patients.”