Abstract
To elucidate the physiological, cellular, and molecular mechanisms responsible for initiating and sustaining ocular neuropathic pain, we created a blue-light-exposure model in C57BL/6 mice. Mice were exposed to 12 h of blue or white light followed by 12 h of darkness. Before blue light exposure, baseline tear secretion, stability, and ocular hyperalgesia were assessed by measuring hyper- or hypo-osmotic solution-induced eye wiping, wind-induced eye closing, and cold-induced eye blinking. At 1 day post-blue light exposure, alterations in hypotonic/hypertonic-induced eye-wiping, and tear film abnormalities were observed. Eye-wiping behaviors were abolished by topical anesthesia. The cold-stimulated eye-blinking and wind-stimulated eye-closing behaviors began after day 3 and their frequency further increased after day 9. Blue-light exposure reduced the density of nerve endings, and increased their tortuosity, the number of beadlike structures, and the branching of stromal nerve fibers, as assessed by whole-mount confocal microscopy. Blue-light exposure also increased TRPV1, but not TRPV4 staining intensity of corneal-projecting neurons in the trigeminal ganglia, as detected by Fluorogold retrograde labeling and immunohistochemistry. TRPV1 and substance P expression was increased, whereas CGRP expression deceased at the mRNA level in isolated corneal projecting neurons. Hence, our blue-light exposure B6 mouse model for assessing tearing and ocular hyperalgesia is useful for studying ocular pain and its underlying mechanisms. Blue-light-induced alterations in tearing and ocular hyperalgesia may be related to the elevated expression of TRPV1, SP, and/or the suppressed expression of CGRP at the ocular surface.