Auricular Electrical Stimulation Alleviates Headache through CGRP/COX-2/TRPV1/TRPA1 Signaling Pathways in a Nitroglycerin-Induced Migraine Rat Model

The study aimed to investigate effect of auricular electrical stimulation (ES) on migraine. Migraine was induced in rats by intraperitoneal administration of nitroglycerin (NTG, 10 mg/kg) three times. Auricular ES pretreatment was performed for five consecutive days. Migraine behaviors were observed by a video recording. Auricular ES pretreatment could reverse the decrease of the total time spent on exploratory (2619.0 ± 113.0 s vs 1581.7 ± 217.6 s, p=0.0029) and locomotor behaviors (271.3 ± 21.4 s vs 114.3 ± 19.7 s, p=0.0135) and also could reverse the increase of the total time spent on resting (19.0 ± 10.6 s vs 154.3 ± 46.5 s, p=0.0398) and grooming (369.9 ± 66.8 s vs 1302.0 ± 244.5 s, p=0.0324) behaviors. Auricular ES pretreatment could increase the frequency of rearing behaviors (38.0 ± 1.8 vs 7.7 ± 3.5, p < 0.0001) and total distance traveled (1372.0 ± 157.9 cm vs 285.3 ± 85.6 cm, p < 0.0001) and also could increase the percentage of inner zone time (6.0 ± 1.6% vs 0.4 ± 0.2%, p=0.0472). The CGRP, COX-2, TRPV1, and TRPA1 immunoreactive cells in the trigeminal ganglion increased in the NTG group compared with the control group (all p < 0.0001); this increase could, however, be reduced by auricular ES pretreatment (27.8 ± 2.6 vs 63.0 ± 4.2, p < 0.0001; 21.7 ± 1.2 vs 61.8 ± 4.0, p < 0.0001; 24.3 ± 1.0 vs 36.5 ± 1.7, p=0.0003; and 20.7 ± 1.9 vs 90.8 ± 6.5, p < 0.0001, respectively). Therefore, we suggest that auricular ES pretreatment is beneficial for the treatment of migraine and this effect is partly related to CGRP/COX-2/TRPV1/TRPA1 signaling pathways.