The Role And Mechanism Of TPRV1 Channel In Rat Dural Inflammation Soup Migraine Model

Background Migraine is a kind of neurological-vascular dysfunction characterized by recurrent and periodic attacks of headache with high prevalence and disability rate.The pathogenesis of migraine has not yet been fully elucidated,and it is currently considered to be a painful disease caused by a sudden change in the in vivo or in vitro environment through the trigeminocervical complex.Transient receptor potential channel subfamily V member 1(TRPV1)belongs to the family of transient receptor channels and is mainly distributed in pain sensory neurons in the brain.The TRPV1 channel has endogenous,exogenous and other activators such as capsaicin.When the channel is activated,calcium ions flow into the cell,triggering a series of cascades that mediate the release of substance P(SP)and calcitonin gene-related peptide(CGRP).SP and CGRP is two downstream molecules in the pathogenesis of migraine,causing activation of the trigeminocervical complex.Aim This study intends to compare the behavioral and biochemical changes of the rats in the dural inflammatory soup migraine model by the activation and blockade of TRPV1 channel,and to further explain the role of TRPV1 channel in the pathogenesis of migraine.Methods Forty adult Sprague-Dawley rats were randomly divided into four groups.The rat migraine model was established by dural inflammatory soup.Rats in each group were given intraperitoneal injection of TRPV1 activator(capsaicin),TRPV1 blocker(capsazepine),CGRP receptor antagonist(CGRP 8-37)or normal saline.The differences of c-Fos and CGRP in trigeminal ganglion(TG),spine trigeminal nucleus caudalis(TNC),C1-C2,rostral ventromedial medulla(RVM),periaqueductal gray(PAG)of each group were compared.The concentration of substance P and CGRP in jugular vein blood were examined.The changes of periorbital pain threshold in rats were analyzed.Results After stimulation with inflammatory soup in the dura mater,the periorbital mechanical pain threshold decreased continuously in the rats.At the 3h time,the pain threshold of capsaicin group was higher than that of normal saline group.The pain threshold of the CGRP receptor antagonist group was higher than that of normal saline group saline group,and was not statistically different from capsazepine group.SP and CGRP concentrations were measured in rat jugular vein blood.The concentrations of SP and CGRP in capsaicin group were higher than those in normal saline group.The SP and CGRP concentrations in capsazepine group were lower than those in normal saline group.The SP and CGRP concentrations in the CGRP receptor antagonist group were lower than those in normal saline group.The SP and CGRP concentration were not statistically different between capsazepine group and CGRP receptor antagonist group.In the brain regions of TG,TNC,C1-C2 and RVM,semi-quantitative immunofluorescence showed that the expression of c-Fos and CGRP in capsaicin group was higher than that in normal saline group.The expression of c-Fos and CGRP in capsazepine group was lower than that in normal saline group.The expression of c-Fos and CGRP in CGRP receptor antagonist group was lower than that in normal saline group.The expression of c-Fos and CGRP in capsazepine group was not statistically different from that in CGRP receptor antagonist group.In PAG,the semi-quantitative results of c-Fos were similar to those in other brain regions.The expression of CGRP in capsaicin group was higher than that in normal saline group.The expression of CGRP in capsazepine group and CGRP receptor antagonist group was lower than that in normal saline group.The expression of CGRP in CGRP receptor antagonist group was lower than that in capsazepine group.Conclusions TRPV1 channel is involved in the pathogenesis of migraine,and its activator can aggravate the nociceptive behavior of the pain,whereas the blockade of TRPV1 can attenuate the nociceptive behavior of the pain,similar to the use of CGRP receptor antagonists.CGRP acts on TG,TNC,C1-C2,RVM,PAG,and these regions participate in the ascending projections of pain pathways.TRPV1 channel receptor antagonists may become new targets for migraine treatment.