The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.

角膜是体内最密集的神经支配和敏感组织。角膜仅受C和A三角纤维的支配，包括由有害机械刺激触发的机械感受器，由机械，化学和热刺激激发的多峰伤害感受器以及通过冷却激活的冷热感受器。有害刺激会激活角膜伤害感受器，其细胞体位于三叉神经节（TG）中，并将中央轴突投射到三叉神经干感觉复合体上。尤其是由角膜神经驱动的眼痛被认为是眼表炎性和创伤性疾病的核心症状。在多种病理情况下，会发生影响角膜神经并导致炎症反应的眼表损伤，例如化学性烧伤，持续性干眼症和角膜神经性疼痛，以及一些眼科手术干预措施（例如光折射手术）后。这篇综述描述了角膜损伤和干眼病（DED）之后的角膜神经末梢的形态和功能变化，这两种眼表状况都会导致感觉异常。另外，讨论了在角膜超敏反应发展中外围和中枢神经免疫相互作用的重要性的最新基础和临床发现。接下来，介绍了由角膜神经异常驱动的TG和中央结构中角膜神经元的细胞和分子变化。