Potential Roles of G Protein-Coupled Receptor 30 (GPR30) in Migraine Pathophysiology

Migraine is a highly prevalent and disabling neurological disorder with multiple hypotheses regarding its pathogenesis. G protein-coupled receptor 30 (GPR30), a member of the G protein-coupled receptor family, was once considered a membrane estrogen receptor. GPR30 is highly expressed in migraine-associated core tissues such as the trigeminal ganglion and exerts an indirect regulatory effect on the pathophysiological processes of migraine, yet there remain controversies over its specific molecular mechanisms and whether it is involved in estrogen-mediated regulation. This review systematically summarizes the latest research advances in the effects of GPR30 on the pathogenesis of migraine, with a focus on the molecular structure, ligand profile, distribution characteristics in the nervous system, related signal transduction pathways of GPR30, as well as its regulatory effects on migraine-associated neural functions. Existing studies have mainly reported the impacts of GPR30 on migraine-related signal pathways and neural functions in neurological diseases, but only verified the correlation between GPR30 and these signal pathways, with contradictory conclusions regarding its regulation of neurovascular functions. In clinical research, there is a lack of evidence from migraine-specific therapeutic clinical trials targeting GPR30, and no estrogen-related evidence chain has been established. Overall, GPR30 may serve as a potential novel target for the prevention and treatment of migraine, and the existing challenges also provide new research perspectives for the development of GPR30-targeted migraine-specific therapies.