Neurobiology of ocular pain

Abstract

Abstract Ocular irritation and pain are associated with many clinical situations (e.g. accidental injury, eye diseases, surgery and contact lens wearing). Pain and related ocular sensations begin with stimulation by injurious stimuli of first-order sensory neurons of the trigeminal ganglion. Neurons responding solely to application in their receptive field of noxious mechanical forces (mechanonociceptive neurons), or of irritant chemicals and heat (polymodal nociceptive neurons), have been identified electrophysiologically in the conjunctiva, cornea, sclera, iris, ciliary body and choroid. The cornea is additionally innervated by neurons responding to low temperatures, which may account for corneal discomfort caused by cold. Also, low-threshold mechanoreceptive and cold-sensitive neurons supply the conjunctiva and sclera, possibly mediating touch and thermal sensations aroused by innocuous stimuli in the front of the eye. Ocular sensory information is transmitted from the trigeminal ganglion to specific higher-order neurons located in the trigeminal brainstem nuclear complex, the thalamus and the cerebral cortex. Local ocular inflammatory responses enhance injury-induced neural activity both in ocular nociceptive terminals and in higher order neurons. In addition to signalling acute lesions, ocular primary sensory neurons participate in post-injury processes, contributing to local inflammatory reactions (neurogenic inflammation) and to the repair of damaged tissues. These effects are mediated at least in part, by substance P and CGRP, two neuropeptides contained in ocular sensory nerve cells that are released peripherally upon tissue damage. Ocular tissues have a trophic interdependence with their sensory neurons. Ocular tissues are the source of neurotrophic factors that are critical for the early development and survival of trigeminal sensory neurons. On the other hand, the morphofunctional integrity of some ocular tissues like the cornea, appears to be dependent on the presence of an intact sensory innervation. Stimulation of ocular sensory pathways by noxious mechanical, chemical and thermal stimulation of cornea, conjunctiva or of other eye structures, evokes distinct types of ocular sensations. Differences in the quality of pain sensation presumably result from the magnitudes of activation of the various sub-populations of ocular nociceptive neurons by different stimulus modalities. In addition to conscious sensations, injurious stimuli evoke protective reflexes (blinking and lacrimation) aimed at protecting the eye and minimizing further ocular damage by noxious stimuli.