Yangxue Qingnao attenuates nitroglycerin-induced chronic migraine-like pain in association with altered mitochondrial calcium handling and reduced TNC neuronal excitability

Chronic migraine is characterized by recurrent trigeminovascular activation, cutaneous allodynia, and central sensitization. Mitochondrial dysfunction and impaired calcium handling may contribute to migraine chronification, but whether these processes are modified by Yangxue Qingnao (YXQN), a traditional Chinese medicine used for headache disorders, remains unclear. Here, a chronic migraine mouse model was induced by intraperitoneal nitroglycerin (NTG) injections on alternate days for 9 days. Migraine-like behaviors, trigeminal nucleus caudalis (TNC) neuropeptide expression, neuronal activation, proteomic profiling, mitochondrial function, and electrophysiological properties were assessed. YXQN attenuated migraine-like phenotypes, reduced TNC calcitonin gene-related peptide (CGRP) levels and c-Fos neuronal activation in TNC region. Proteomic analysis identified exploratory changes in mitochondrial- and calcium-transport-related pathways. YXQN treatment was accompanied by improvements in selected mitochondrial structural and functional measures, reduced calcium-associated fluorescence signals, and attenuated TNC neuronal hyperexcitability. These findings support further investigation of mitochondrial calcium handling and TNC neuronal excitability as potential contributors to the effects of YXQN.