Ocular discomfort and
eye pain are frequently reported by patients with
dry eye disease (DED), and their management remains a real therapeutic challenge for the Ophthalmologist. In DED patients, injury at the level of each structure of the ocular surface can determine variable symptoms, ranging from mild ocular discomfort up to an intolerable
pain evoked by innocuous stimuli. In refractory cases, the persistence of this harmful signal is able to evoke a mechanism of maladaptive plasticity of the nervous system that leads to increased
pain responsiveness. Peripheral and, subsequently, central sensitization cause nociceptor hyperexcitability and persistent pain perception that can culminate in the paradoxical situation of perceiving
eye pain even in the absence of ocular surface abnormalities. Effective therapeutic strategies of these cases are challenging, and new options are desirable. Recently, a theoretical novel therapeutic approach concerns
enkephalins thanks to the evidence that
eye pain sensations are modulated by endogenous
opioid peptides (
enkephalins,
endorphins and
dynorphins). In this regard, new topical agents open up a new theoretical scenario in the treatment of ocular discomfort and
eye pain in the setting of DED, such as, for example, a multimolecular complex based on
proteins and
glycosaminoglycans also containing
opiorphin that may assist the physiological
pain-relieving mechanism of the eye.