This sensory information is processed at various levels of the neuroaxis, finally reaching different areas of the cerebral cortex where it evokes pain sensations and unpleasant feelings referred to the eye, which persist for a variable period of time until healing takes place. These produce a discharge of nerve impulses that travel to the brain, encoding the spatial, and temporal characteristics of the noxious stimuli. External physical or chemical stimuli acting on the eye at intensities near or over the level required to cause cell damage, stimulate a specific set of peripheral sensory nerve fibers generically named nociceptors. The most obvious origin of eye pain is acute local injury. Hence, the pain experience constitutes a highly distributed and complex brain function. These are subjected to intrinsic control by cortical, subcortical, and midbrain modulatory networks.

Processing of the sensory-discriminative and affective-motivational features of pain is performed along the brainstem and multiple upper brain structures. They have a compelling arousing and directive nature, comprising reflex responses, and complex behavioral reactions. The affective-motivational neural mechanisms of pain produce the accompanying emotional distress, which may have different quality and intensity. Sensory-discriminative nervous mechanisms map the origins of damaging events (mechanical, chemical, thermal) along with their location, their intensity and temporal aspects of the experience. The qualitative and quantitative components of the pain experience vary, reflecting the complexity of the underlying peripheral and central neural processes. The growing number of eye surface manipulations in the clinics (surgery, contact lenses) and the frequent exposure to artificial environments (air conditioning, video display terminals, air pollutants) is renewing the interest of eye care professionals for a better understanding of ocular pain. Nevertheless, pain is a symptom in a variety of other ocular pathologies, in particular those affecting tissues of the anterior segment of the eyeball and the orbit. In the eye, diseases leading to impaired vision such as cataract, retinal detachment or degeneration, or open-angle glaucoma course without pain, in spite of the accompanying damage to important eye structures. Pain has been defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. In uncomplicated photorefractive surgery and moderate dry eye, cold thermoreceptors appear to be mainly affected, evoking predominant sensations of unpleasant dryness. When inflammation dominates (allergic or actinic kerato-conjunctivitis), polymodal nociceptors are primarily stimulated and sensitized, causing pain. Eye diseases or ocular surface surgery cause different levels of inflammation and/or nerve injury, which in turn activate sensory fibers of the eye in a variable degree. This malfunction evokes ‘neuropathic pain’ which may also result from abnormal function of higher brain structures where ocular TG neurons project. When trauma, infections, or metabolic processes directly damage eye nerve terminals, these display aberrant impulse firing due to an abnormal expression of transducing and excitability-modulating ion channels. During chronic inflammation, additional, long-lasting changes in the expression and function of stimulus-transducing and voltage-sensitive ion channels develop, thereby altering polymodal terminal’s excitability and evoking chronic inflammatory pain. Mediators released by local inflammation, increase the excitability of eye polymodal nociceptors causing their sensitization and the augmented pain sensations. Pricking pain is evoked by mechano-nociceptors, while polymodal nociceptors are responsible of burning and stinging eye pain sensations of dryness appear to be mainly evoked by cold thermoreceptors.

Their distinct sensitivity to stimulating forces is determined by the expression of specific classes of ion channels: Piezo2 for mechanical forces, TRPV1 and TRPA1 for heat and chemical agents, and TRPM8 for cold. Polymodal nociceptors also respond to heat, exogenous irritants, and endogenous inflammatory mediators, whereas cold thermoreceptors detect moderate temperature changes. Mechano-nociceptors are only excited by noxious mechanical forces. Normal or physiological pain results of the stimulation by noxious stimuli of sensory axons of trigeminal ganglion (TG) neurons innervating the eye. Eye pain is an unpleasant sensory and emotional experience including sensory-discriminative, emotional, cognitive, and behavioral components and supported by distinct, interconnected peripheral and central nervous system elements.

Warm eye compress causes vasodilation