Oxidative Stress and Mitophagy in Rats With Nitroglycerin/Inflammatory Soup-Induced Migraine: A Comparative Study

Oxidative stress leads to mitochondrial DNA, protein, and lipid damage, ultimately resulting in mitochondrial dysfunction. Decreased mitophagy leads to the continuous accumulation of damaged mitochondria, which further induces oxidative stress and cellular damage. Mitochondrial dysfunction and an imbalance between energy supply and demand may lead to increased migraine susceptibility. However, there have been no comparative studies from the perspective of oxidative stress and mitophagy.

Male Sprague-Dawley rats were divided into control, NTG (10 mg/kg, intraperitoneal, Days 1/3/5/7), and IS (epidural infusion, 7 days) groups (n = 10, per group). Paw mechanical thresholds, migraine-like behaviors (head-face scratching, body grooming, exploration, and freezing time), and oxidative markers (malondialdehyde, catalase, reduced glutathione, and superoxide dismutase) in the trigeminal nucleus caudalis were assessed. The expressions of PINK1, Parkin, LC3II/I, TOMM20, and COXIV were evaluated to quantify levels of mitophagy.

Both NTG/IS models reduced mechanical thresholds, but NTG induced stronger head scratching and freezing time. Oxidative stress markers diverged: NTG elevated malondialdehyde and depleted reduced glutathione/superoxide dismutase, while IS primarily reduced superoxide dismutase. Both models exhibited a decreased LC3II/I ratio as well as reduced PINK1 and Parkin.

NTG/IS administration comparatively decreased the mechanical threshold, increased the level of oxidative stress, and decreased the level of mitophagy in the trigeminal nucleus caudalis in migraine rats.