Oral Communications

OpenAlex İngilizce

Aim: Mast cell (MC) degranulation play key role in migraine pathophysiology by inducing dural neurogenic inflammation.It was reported that endocannabinoids could prevent neurogenic inflammation but related mechanisms have not yet been clarified.We aimed to investigate effects of methanandamide and cannabinoid receptors on mast cell degranulation mediatedneurogenic inflammation induced by MC secretagogue compound-48/80.Methods: In-vivo and ex-vivo rat groups (n=7) were intraperitoneally and topically administered saline, compound-48/80 (2 mg/kg), methanandamide (20 mg/kg), cromolyn (50 mg/kg) + compound-48/80, methanandamide + compound-48/80, rimonabant (2 mg/kg) + methanandamide + compound-48/80, capsazepine (10 mg/kg) + methanandamide + compound-48/80.Neurogenic inflammation markers including calcitonin gene-related peptide (CGRP) and substance-P(SP) levels in plasma, brainstem and brain samples were measured using ELISA.Ex-vivo dural MC numbers and degranulations were determined.Data were analyzed with One-Way ANOVA.Results: Compound-48/80 increased CGRP and SP levels in plasma, brainstem and brain (p<0.05),these increasements were prevented by cromolyn and methanandamide (p<0.05).Rimonabant blocked effect of methanandamide (p<0.05) but capsazepine had no effect.Methanandamide decreased MC degranulation induced by compound-48/80 in ex-vivo group (p<0.05). Conclusions:MC degranulation causes neurogenic inflammation by inducing CGRP and SP release in plasma, brainstem and brain.Methanandamide ameliorates neurogenic inflammation by stabilizing dural MCs, as well as by attenuating CGRP and SP release through cannabinoid-1 receptors in brainstem and brain.Endocannabinoids and their receptors may be new targets for migraine treatment.