Lacosamide inhibits calcitonin gene-related peptide production and release at trigeminal level in the rat

M. C. Greco, A. Capuano, P. Navarra, G. Tringali

Research output: Contribution to journalArticlepeer-review

Abstract

Background Several classes of drugs are effective in prevention and treatment of migraine, although they may differ among each other in their mode of action and in indications. One such class is represented by antiepileptics. Lacosamide is an approved antiepileptic drug that also shows antinociceptive activity in animal models, including analgesic efficacy in central and trigeminal pain. Calcitonin gene-related peptide (CGRP) is considered the main neuro-mediator of trigeminal signalling, playing an essential role in headache, migraine in particular. Here, we investigated the effects of lacosamide on CGRP signalling in both in vitro and ex vivo/vitro models in the rat. Methods We assessed: (1) CGRP released from brainstem explants at baseline or after pharmacological challenges; and (2) CGRP levels in brain areas after in vivo treatments with test drugs. Results We found that: (1) lacosamide inhibits CGRP release from brainstem explants under basal conditions as well as after stimulation by 56 mM KCl, 10 μM veratridine or 1 μM capsaicin; and (2) the i.p. administration of nitroglycerine produces an increase in CGRP levels in the brainstem and trigeminal ganglia, which is inhibited by a pre-treatment with lacosamide. Conclusions These findings provide preliminary evidence suggesting that lacosamide is able to control pain transmission under conditions affecting the trigeminal system, such as migraine.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalEuropean Journal of Pain (United Kingdom)
Volume20
Issue number6
DOIs
Publication statusPublished - Jul 1 2016

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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