AMPARs参与调控口颌面部疼痛的研究进展  

Research progress on AMPARs involved in regulating orofacial pain

作　　者：张宇晗 王航[1] 沈颉飞[1] ZHANG Yuhan;WANG Hang;SHEN Jiefei(Department of Prosthodontics,West China Hospital of Stomatology Sichuan University&National Clinical Research Center for Oral Diseases&State Key Laboratory of Oral Diseases,Chengdu 610041,China)

机构地区：[1]四川大学华西口腔医院修复科、国家口腔疾病临床研究中心、口腔疾病国家重点实验室,四川成都610041

出　　处：《口腔疾病防治》2023年第12期907-912,共6页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(81870800、82071149)。

摘　　要：口颌面部疼痛的发病率高且病理机制复杂。目前临床缺乏持久有效的治疗药物,给患者及社会带来巨大的经济负担。因此,研发更加持久有效的治疗药物具有重要意义。近年来,大量证据表明α⁃氨基⁃3⁃羟基⁃5⁃甲基⁃4⁃异恶唑丙酸受体(α⁃amino⁃3⁃hydroxy⁃5⁃methyl⁃4⁃isoxazolepropionic acid receptors,AMPARs)的激活在促进躯体和口颌面部疼痛中起着至关重要的作用。其中,蛋白激酶调节亚基磷酸化及辅助蛋白相互作用等促进AMPARs的激活与转运和信号转导,从而调控AMPARs的表达。含GluA1的AMPARs的增加可促进钙离子内流,进一步激活蛋白激酶及辅助蛋白,形成自反馈环,这是促进慢性疼痛的重要机制。其次,AMPARs在三叉神经系统与脊髓神经系统中表达类似,上述调控也可参与调控口颌面部炎性疼痛。然而,在口颌面部神经病理性疼痛、癌性疼痛中AMPARs的调控研究相对不足,未来需要更深入的研究。此外,AMPARs拮抗剂治疗疼痛尚缺乏临床证据。了解AMPARs的激活与转运的调控机制,精准干预AMPARs的激活与转运,可为研发新型镇痛药提供有效策略,从而为临床上治疗口颌面部疼痛提供新思路。The incidence of orofacial pain is high,and its pathological mechanism is complex.Currently,there is a lack of longlasting and effective clinical treatment drugs,resulting in a major economic burden to patients and society.Therefore,it is important to develop more durable and effective drugs for treatment.In recent years,substantial evidence has shown thatαamino3hydroxy5methyl4isoxazolepropionic acid receptors(AMPARs)play a vital role in somatic and orofacial pain.Among them,subunit phosphorylation regulated by protein kinases and interactions with partner proteins promote the activation and trafficking of AMPARs and signal transduction to regulate the expression of AMPARs.The increase of GluA1containing AMPARs promotes calcium ion influx,further activating protein kinases and auxiliary proteins,which forms a selffeedback loop.This is an important mechanism that promotes chronic pain.The expression of AMPARs in the trigeminal nervous system and the spinal cord nervous system overlaps,and the above mechanism may also participate in regulating orofacial pain.However,research on AMPARs in orofacial neuropathic pain or cancerrelated pain is relatively insufficient,and more indepth research is needed in the future.Furthermore,there is a lack of clinical evidence for AMPAR antagonists to treat pain.Understanding the regulatory mechanisms of the activation and trafficking of AMPARs and precisely intervening in the activation and trafficking of AMPARs may provide effective strategies for the development of new analgesics and offer new insights for treating orofacial pain.

关 键 词：口颌面部疼痛 α⁃氨基⁃3⁃羟基⁃5⁃甲基⁃4⁃异恶唑丙酸受体 结构特征 激活与转运 蛋白激酶 磷酸化 蛋白互作 拮抗剂 

分 类 号：R78[医药卫生—口腔医学]