Investigation of the antinociceptive and anti-neuroinflammatory effects of luteolin in invivo and ex-vivo rat models of migraine

This study aimed to examine the impact of luteolin on pain behavior and migraine mechanisms using in-vivo and ex-vivo migraine models in rats. In vivo, different doses of luteolin and the migraine drug sumatriptan were administered intraperitoneally to rats alone and in various combinations for 3 days. On the third day, 30 min after the last injections, the migraine model was established by NTG injection. In ex-vivo experiments, NTG, luteolin and sumatriptan were treated to hemiskull preparations alone and in different combinations. Pain sensitivity was assessed by von-Frey test. Meningeal mast cells were stained with toluidine blue and evaluated for number and degranulation. CGRP concentrations in trigeminal ganglia and ex-vivo supernatant samples, and brainstem CGRP and c-Fos concentrations were measured by ELISA. Data were analyzed by one-way or repeated measures ANOVA test. In vivo, luteolin alleviated NTG-induced mechanical hyperalgesia, brainstem c-Fos and trigeminal ganglion CGRP expression, and mast cell activation (p<0.01) but not brainstem CGRP expression and mast cell number. Luteolin also reduced NTG-induced CGRP release from ex-vivo preparations (p<0.05). Sumatriptan, as a positive control, prevented the NTG- evoked changes (p<0.01). Luteolin ameliorates pain behavior, c-Fos levels, and components of the neurogenic inflammation underlying migraine (such as CGRP and mast cell activation) in experimental migraine conditions. Our findings suggest that luteolin may be a promising candidate for the treatment of migraine in the future.