Effect Of Flunarizine And Topiramate On NALP3 Inflammasome In Trigeminal Ganglion Of Rat Migraine Model

Background:Migraine is a complex nerve vascular disorder affecting 10%～20%of general population,it not only affects the patient’s quality of life,but also brings heavy economic burden for the family and society,the prevention and treatment of migraine is urgent.The pathogenesis of migraine is not clear at the moment,studies have shown that inflammatory activation and sensitization of primary sensory neurons that innervate the meninges and related blood vessels is thought to be the basis of migraine.Nucleotide-binding oligomerization domain-like receptor protein 3(NALP3 or NLRP3)inflammasome cascade reaction and the processing of interleukin 1β(IL-1β)may be involved in the pathophysiological process of headache(including migraine)induced by inflammatory dural stimulation.Flunarizine and topiramate are evidence-based prevention for migraine,however,there are few studies about the effect of flunarizine and topiramate on NALP3 inflammasome and interleukin 1β.Objective:To explore whether flunarizine and topiramate affect the expressions of NALP3 inflammasome and interleukin 1β in trigeminal ganglion of rat migraine model induced by inflammatory dural stimulation.Methods:Fifteen healthy adult male SD rats were randomly divided into blank group,saline group and 7-day inflammatory group(5 in each group).Von Frey Filaments were used to test the pain threshold of periorbital skin.Expressions of NALP3 inflammasome and IL-1β in trigeminal ganglion of different groups were detected by Western blot.Forty-five adult male SD rats were randomly divided into prevention control group,0.5 mg/kg flunarizine group,1 mg/kg flunarizine group,2 mg/kg flunarizine group,4 mg/kg flunarizine group,10mg/kg topiramate group,30mg/kg topiramate group,60mg/kg topiramate group,90mg/kg topiramate group(5 in each group).Expressions of NALP3 inflammasome and IL-1β in trigeminal ganglion of different groups were detected by Western blot.Expressions of NALP3 inflammasome and IL-1β in trigeminal ganglion of prevention control group,2 mg/kg flunarizine group and 60mg/kg topiramate group(5 in each group)were also detected by immunofluorescence.Results:The periorbital pain threshold was significantly lower in 7-day inflammatory group than in saline group(P<0.05).The expression levels of NALP3,pro-caspase-1,caspase-1 and IL-1β were significantly higher in 7-day inflammatory group than in saline group(P<0.05).The expression levels of NALP3,pro-caspase-1,caspase-1 and IL-1β were significantly lower in 2 mg/kg and 4 mg/kg flunarizine groups than in prevention control group(P<0.05).The expression levels of NALP3,pro-caspase-1,caspase-1 and IL-1β were significantly lower in 60mg/kg and 90mg/kg topiramate groups than in prevention control group(P<0.05).The fluorescence intensity of NALP3,caspase-1,IL-1β was significantly lower in 2mg/kg flunarizine group and 60mg/kg topiramate group than in prevention control group.Conclusion:Flunarizine and topiramate might protect against migraine by inhibiting the synthesis of NALP3 inflammasome and IL-1β in trigeminal ganglion,and the role in inhibiting inflammation of trigeminal primary sensory neurons may be one of the important mechanisms for the prevention of migraine.