Effect of Alpha Lipoic Acid on hyperemia and trigeminovascular nociceptive activity induced by cortical spreading depression

Abstract

Objective Cortical spreading depression (CSD) is a phenomenon associated with migraine attack, which can cause cerebral hyperemia and activation of the trigeminovascular nociceptive system. Alpha-lipoic acid (ALA) was reported to have the potential of reducing attack frequency in migraine patients. However, the underlying mechanism was unclear. This study aimed to investigate the effects of ALA on cerebral hyperemia and activation of the trigeminovascular nociceptive system in a CSD migraine animal model.

Methods Wistar rats were divided into 7 groups: control group, CSD group, 4 CSD with ALApretreated groups, and a sumatriptan-pretreated group. pretreated groups received intravenous injection (i.v.) of saline or ALA at 10, 30, 100 or 300 mg/kg bodyweight 30 minutes before CSD induction or sumatriptan at 0.4 mg/kg bodyweight 5 minutes before CSD induction by placing 3 mg of solid potassium chloride (KCl) on the right parietal cortex. Cerebral blood flow was monitored using a laser Doppler flowmeter for 2 hours. After blood flow measurement, brain tissue was collected for c-Fos staining at the trigeminal nucleus caudalis (TNC).

Results Application of KCl produced a series of hyperemia peak characteristics of CSD. ALA pretreatment reduced amplitude and the number of hyperemic peaks, and increased the period (peak-to-peak duration), similar to sumatriptan pretreatment. Furthermore, 30, 100, and 300 mg/kg body weight of ALA showed a larger reduction of c-Fos positive cells than sumatriptan at the TNC.

Conclusion ALA pretreatment reduces CSD-induced cerebral hyperemia and activation of the trigeminovascular nociceptive system. These findings support the role of ALA as a prophylactic drug for migraine headache.