Giannaccare Giuseppe, Ghelardini Carla, Mancini Alessandra, Scorcia Vincenzo, Di Cesare Mannelli Lorenzo
Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy.
J Clin Med. 2021 Dec 25;11(1):108. doi: 10.3390/jcm11010108.
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.
干眼症（DED）患者经常报告眼部不适和眼痛，对眼科医生来说，对其进行治疗仍然是一项真正的挑战。在干眼症患者中，眼表各结构层面的损伤可导致不同症状，从轻微的眼部不适到无害刺激引发的难以忍受的疼痛。在难治性病例中，这种有害信号的持续存在能够引发神经系统的适应性不良可塑性机制，导致疼痛反应性增加。外周敏化以及随后的中枢敏化会导致伤害感受器过度兴奋和持续的疼痛感知，甚至在没有眼表异常的情况下也可能导致感知到眼痛这种自相矛盾的情况。对这些病例进行有效治疗具有挑战性，因此需要新的治疗选择。最近，一种新的理论性治疗方法涉及脑啡肽，因为有证据表明眼部疼痛感觉受内源性阿片肽（脑啡肽、内啡肽和强啡肽）调节。在这方面，新型局部用药为干眼症患者眼部不适和眼痛的治疗开辟了新的理论前景，例如，一种基于蛋白质和糖胺聚糖且还含有阿片样肽的多分子复合物，它可能有助于眼睛的生理性止痛机制。
