Papers of the Week

Migraine is a common brain disorder characterized by recurrent episodes of headache. It is a complex and multifactorial disease with a higher prevalence in females than in males. Several risk factors have been associated to migraine disease as genetic factors, sex and age. The pathophysiology of migraine is still unclear; however, it has been proven that NOD-like receptor protein 3 (NLRP3) inflammasome pathway overactivation as well as p-ERK/p-CREB axis contribute to migraine pathogenesis. Therefore, the aim of this study was to investigate the effect of BAY-117082, a NLRP3 inflammasome inhibitor and p-ERK/p-CREB modulator, in an in vivo model of nitroglycerin (NTG)-induced migraine. Migraine model was induced by NTG intraperitoneal administration at dose of 10 mg/kg diluted in 0.9% saline. Mice were treated intraperitoneally with BAY-117082 at doses of 1 mg/kg, 5 mg/kg, and 10 mg/kg, 5 minutes after NTG injection. Mice were sacrificed 4 h following NTG injection; the whole brain with the rostral spinal cord was removed to perform several analysis. Our results demonstrated that, following behavioral tests for pain and photophobia, BAY-117082 treatment at doses of 5 mg/kg and 10 mg/kg reduced pain attacks induced by NTG more than BAY-117082 at the dose of 1 mg/kg. Moreover, the treatment with BAY-117082 at doses of 5 mg/kg and 10 mg/kg significantly reduced histological damage in the trigeminal nerve nucleus and significantly decreased inflammosome activation by reduction of NLRP3, ASC, IL-1β and TNF-α expression. Additionally, the treatment with BAY-117082 at doses of 5 mg/kg and 10 mg/kg significantly modulated p-ERK/p-CREB axis activation through the reduction of p-ERK, p-AKT, p-CREB and p-PI3K expression. Therefore, the obtained results offer new insight into the role of NLRP3 inflammasome pathway and p-ERK/p-CREB axis in migraine pathogenesis, suggesting that BAY-117082 could be considered a novel therapeutic strategy to treat migraine.