New Perspectives in the Pathophysiology and Treatment of Pain in Patients with Dry Eye Disease.

Giuseppe Giannaccare,Alessandra Mancini,Carla Ghelardini,Lorenzo Di Cesare Mannelli,Vincenzo Scorcia

doi:10.3390/jcm11010108

Giuseppe Giannaccare, Alessandra Mancini + Show 3 more

Open Access

https://doi.org/10.3390/jcm11010108

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Abstract

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.

Highlights

Dry eye disease (DED) is a multifactorial condition occurring due to reduced tear production, excessive tear evaporation or both
The aim of this review is to summarize the emerging role of opiorphin in the control of ocular discomfort and eye pain
The greater balance between analgesia and side effects guaranteed by opiorphin is undoubtedly due to its ability to activate opioid pathways by inhibiting the destruction of endogenous enkephalins released in response to a painful stimulus [30,38]

Summary

Introduction

Dry eye disease (DED) is a multifactorial condition occurring due to reduced tear production (hyposecretive DED), excessive tear evaporation (evaporative DED) or both (mixed DED). The increase in osmolarity, in turn, causes damage to the epithelial cells of the conjunctiva and cornea, as well as to the goblet cells that produce the normal mucous component of tears, and induces an inflammatory reaction at the level of the entire ocular surface [3] Med. 2022, 11, 108 induces an inflammatory reaction at the level of the entire ocular surface [3] These alterations trigger a vicious circle that aggravates the condition of DED, and determines the chronicization thecondition process, with damage of the nervethe fibers that conductofthe to that aggravatesofthe of DED, and determines chronicization thestimuli process, the main lacrimal the that production thestimuli tear film [3].main. The aim of this review is to summarize the emerging role of opiorphin in the control of ocular discomfort and eye pain

Ocular Discomfort and Eye Pain

Opiorphin

Conclusions