ABSTRACT
@#The incidence of orofacial pain is high, and its pathological mechanism is complex. Currently, there is a lack of long-lasting 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 that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 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 GluA1-containing AMPARs promotes calcium ion influx, further activating protein kinases and auxiliary proteins, which forms a self-feedback 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 cancer-related pain is relatively insufficient, and more in-depth 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.