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Mitochondrial dysfunction in trigeminal ganglion contributes to nociceptive behavior in a nitroglycerin-induced
Xin-Ying Guan1,2, Xin Dong3, Yi-Xuan Wang1,2
1Department of Neurology, the Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China.
Abstract:
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.
Insights
Mitochondrial dysfunction in trigeminal nerves contributes to migraine pain by altering calcium signaling. Targeting mitochondrial function may alleviate migraine symptoms.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Pain Research
Background:
- Migraine is a complex neurological disorder with unclear diagnostic and management pathways.
- Mitochondrial dysfunction and trigeminal nerve activity are implicated in migraine pathogenesis.
- Understanding these mechanisms is crucial for developing effective migraine treatments.
Purpose of the Study:
- To investigate the role of mitochondrial dysfunction and calcium signaling in trigeminal neurons in a mouse model of migraine.
- To examine the impact of nitroglycerin (NTG)-induced migraine on trigeminal ganglion (TG) cellular processes.
- To explore potential therapeutic targets by assessing the effect of modulating mitochondrial function on migraine symptoms.
Main Methods:
- Establishment of a murine migraine model using intraperitoneal administration of nitroglycerin (NTG).
- Assessment of behavioral changes using the open field test to evaluate allodynia and sensory processing.
- Measurement of calcium signaling in TG neurons following adenosine triphosphate (ATP) stimulation.
- Quantification of mRNA levels for key mitochondrial biogenesis genes (Nrf1, Nrf2, Pgc-1) in the TG.
Main Results:
- NTG-treated mice displayed significant periorbital allodynia and altered exploratory behavior.
- Increased calcium signaling was observed in TG neurons from NTG-treated mice.
- Downregulation of Nrf1, Nrf2, and Pgc-1 mRNA levels in the TG of migraine model mice.
- Pharmacological interventions targeting mitochondrial function modulated NTG-induced migraine pain.
Conclusions:
- Mitochondrial dysfunction in TG neurons plays a critical role in regulating mechanical hyperalgesia in an NTG-induced migraine model.
- Aberrant calcium signaling in trigeminal neurons is a key downstream effect of mitochondrial dysfunction in migraine.
- Modulating mitochondrial function presents a promising therapeutic strategy for managing chronic migraine pain.
