Metoclopramide inhibits trigeminovascular activation: evidence for effective acute attack treatment in migraine

Authors: HACER DOĞANAY AYDIN, DOĞA VURALLI, DİDEM TUBA AKÇALI, HAYRUNNİSA BOLAY BELEN

Abstract: Background/aim: Metoclopramide is an effective and commonly used medication in acute migraine treatment but an experimental evidence base is lacking. We aimed to investigate the antimigraine effect of metoclopramide in a migraine model and whether the analgesic effect of metoclopramide was likely to be D₂ receptor-mediated. Materials and methods: Cortical spreading depression (CSD) was used to model migraine in adult male Wistar rats. Five CSDs were induced by pinprick. Metoclopramide (two different doses), raclopride, or 0.9% saline were administered 30 min before CSD induction. Two hours after the experiments, brain tissues were examined for c-fos activation. Results: In metoclopramide groups brain stem c-fos expression was significantly lower than in the CSD side of the saline group (P = 0.002). In the raclopride group, ipsilateral brain stem c-fos expression was also lower than in the saline group (P = 0.002). No difference in c-fos expression in the ipsilateral trigeminal nucleus caudalis between the raclopride and metoclopramide groups was observed (P > 0.05). Conclusion: Metoclopramide is shown to suppress trigeminovascular activation for the first time, providing an experimental basis for its role in migraine. The analgesic effect of metoclopramide is likely to be mediated by D₂ receptors since raclopride, a selective D₂ receptor antagonist, suppresses trigeminovascular activation similarly.

Keywords: Metoclopramide, trigeminal nucleus caudalis, D₂ receptors, raclopride, trigeminovascular system, migraine, rat

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