School of Optometry & Vision Science, University of New South Wales, Sydney, New South Wales, Australia.
J Neurosci Res. 2024 Jan;102(1):e25285. doi: 10.1002/jnr.25285.
The altered activity generated by corneal neuronal injury can result in morphological and physiological changes in the architecture of synaptic connections in the nervous system. These changes can alter the sensitivity of neurons (both second-order and higher-order projection) projecting pain signals. A complex process involving different cell types, molecules, nerves, dendritic cells, neurokines, neuropeptides, and axon guidance molecules causes a high level of sensory rearrangement, which is germane to all the phases in the pathomechanism of corneal neuropathic pain. Immune cells migrating to the region of nerve injury assist in pain generation by secreting neurokines that ensure nerve depolarization. Furthermore, excitability in the central pain pathway is perpetuated by local activation of microglia in the trigeminal ganglion and alterations of the descending inhibitory modulation for corneal pain arriving from central nervous system. Corneal neuropathic pain may be facilitated by dysfunctional structures in the central somatosensory nervous system due to a lesion, altered synaptogenesis, or genetic abnormality. Understanding these important pathways will provide novel therapeutic insight.
角膜神经元损伤产生的改变活动可导致神经系统中突触连接结构的形态和生理变化。这些变化可改变投射疼痛信号的神经元（包括二级和更高级别投射神经元）的敏感性。一个涉及不同细胞类型、分子、神经、树突细胞、神经激肽、神经肽和轴突导向分子的复杂过程导致了高水平的感觉重新排列，这与角膜神经病理性疼痛发病机制的所有阶段都有关。迁移到神经损伤区域的免疫细胞通过分泌神经激肽来协助产生疼痛，这些神经激肽可确保神经去极化。此外，三叉神经节中小胶质细胞的局部激活以及从中枢神经系统到达角膜疼痛的下行抑制调节的改变，可使中枢疼痛通路的兴奋性持续存在。由于损伤、突触发生改变或遗传异常，中枢躯体感觉神经系统的功能障碍结构可能会促进角膜神经病理性疼痛。了解这些重要途径将提供新的治疗见解。
