Mitochondrial dysfunction in trigeminal ganglion contributes to nociceptive behavior in a nitroglycerin-induced migraine mouse model.

Migraine is a chronic episodic neurological disorder. However, its diagnosis and management remain unclear. The pathogenesis of migraine is intricately linked to the dysfunction of mitochondria and aberrant trigeminal neuronal activity. Here, we established a murine migraine model via intraperitoneal administration of nitroglycerin (NTG) to examine alterations in mitochondria-associated proteins and calcium signaling patterns within trigeminal neurons, while also investigating the underlying mechanisms. NTG-treated mice exhibited marked periorbital allodynia, decreased crossing of the central area, and decreased time spent in the central area in the open field test compared to Veh treated animals. Furthermore, increased calcium signaling in response to adenosine triphosphate (ATP) stimulation was observed in the trigeminal ganglion (TG) of mice with migraine. Meanwhile, mRNA levels of genes including nuclear respiratory factor-1 (Nrf1), nuclear respiratory factor-2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1) were decreased in the TG. Pharmacological regulation of the mitochondrial function affected NTG-induced migraine chronic pain symptoms. TG mitochondria dysfunctions is implicated in the regulation of mechanical hyperalgesia through the modulation of calcium signaling in an NTG-induced migraine animal model.