Abstract

Chronic migraine with aura (CMA) is a debilitating neurological disorder, yet the underlying cellular and molecular mechanisms linking behavioral manifestations to neurochemical changes remain incompletely understood. This study investigates the behavioral correlates of CMA in a rat model, focusing on the interplay between systemic oxidative stress and the neuropeptide Calcitonin Gene-Related Peptide (CGRP). CGRP is a potent vasodilator and neurotransmitter whose receptor signaling, often involving the CGRP receptor (CGRP-R) on the plasma membrane of trigeminal neurons, is central to migraine pathophysiology. We established a chronic migraine with aura model in rats and assessed behavioral metrics (e.g., allodynia, photophobia) alongside biochemical markers of oxidative stress (e.g., malondialdehyde, superoxide dismutase activity) and CGRP levels in the trigeminal ganglion and plasma. Our findings reveal a significant correlation between increased CGRP expression and elevated oxidative stress markers, which, in turn, strongly correlate with the severity of migraine-like behaviors. Specifically, elevated CGRP levels may exacerbate neuronal excitability and neurogenic inflammation, potentially by modulating ion channel activity and membrane integrity under conditions of high oxidative load. These results underscore the critical role of the CGRP-oxidative stress axis in the cellular pathology of CMA, providing novel targets for therapeutic intervention aimed at stabilizing neuronal membrane function and reducing chronic pain.