Ma Lulin, Sun Dongdong, Wen Song, Yuan Jie, Li Jing, Tan Xinran, Cao Song
Department of Pain Medicine, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, Guangdong, China.
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Mol Neurobiol. 2025 Mar;62(3):3361-3375. doi: 10.1007/s12035-024-04485-x. Epub 2024 Sep 16.
Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.
慢性疼痛作为一个社会公共卫生问题，对患者的生活质量有严重影响。目前，用于治疗慢性疼痛的主要药物是阿片类药物、解热药和非甾体抗炎药（NSAIDs）。但明显的副作用限制了它们的使用，因此迫切需要寻找新的治疗靶点。突触后致密物（PSD）-95蛋白在慢性疼痛的发生和发展中起重要作用。PSD-95蛋白的过度表达及其与其他蛋白的相互作用与慢性疼痛密切相关。此外，已证实抑制PSD-95表达以及与其他蛋白相互作用的PSD-95相关药物能显著治疗慢性疼痛。总之，尽管未来还需要更深入的研究，但这些研究表明，PSD-95及其相关蛋白，如N-甲基-D-天冬氨酸受体（NMDAR）亚基2B（GluN2B）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）、钙调蛋白依赖性蛋白激酶II（CaMKII）、5-羟色胺2A受体（5-HT2AR）和神经元型一氧化氮合酶（nNOS），是慢性疼痛有前景的治疗靶点。
