Behavioral Correlates of Migraine, Oxidative Stress, and CGRP Levels in the Experimental Model of Chronic Migraine with Aura in Rats

Migraine is a common chronic neurovascular disease accompanied by unilateral headache, photophobia, allodynia, and autonomic disturbances. About 1/3 of migraine patients have a transient neurological deficit that precedes or overlaps the headache phase, called aura. The main physiological mechanism underlying aura is thought to be cortical spreading depression (CSD), a wave of massive depolarization passing through neurons and glial cells of the cortex. The aim of the present study was to develop the model of chronic migraine with aura in rats and analyze the main behavioral and biochemical correlates of migraine. Male rats were subjected to surgery with the installation of a mini bath providing access to the dura mater above the somatosensory cortex. KCl was applied on the dura mater to induce CSD every other day for 9 days. Sham rats obtained NaCl application according to the same protocol. Behavioral tests were performed before and after application of KCl or NaCl. Repeated KCl application decreased locomotor and exploratory activity, as well as cognitive ability, increased anxiety and induced photophobia and allodynia in rats. Besides, rats with a model of chronic migraine with aura showed increased plasma calcitonin gene-related peptide (CGRP) concentration and decreased glutathione peroxidase activity in brain tissue. In conclusion, the proposed model can be used to study the behavioral correlates of chronic migraine with aura in experimental animals, which will allow us to investigate the underlying mechanisms and develop treatment approaches.