IL-6 Contributes To Nav1.3 Up-regulation In Trigeminus A Mechanism Study Of Trigeminal Neuralgia

Introduction Although the vascular compression and demyelination of the cranial nerve root have been proved to be the etiology of TN,the exact pathogenesis has been still unknown.This study focused on the effects of inflammatory factors and sodium channels on development of the ectopic impulse in the trigeminal nerve.Method The serum level of IL-1β,IL-2,IL-6,IL-8,TNF-α and IFN-γ in TN patients were detected using Elisa,and the relationship between their levels and the severity of TN were analyzed.The TN model was established by means of the infraorbital nerve chronic constriction injury.The mechanical pain threshold of the rat at different postoperative time points was tested and the pathology of the nerve was examined.Then,the trigeminal nerve fibers at the compression site(ION),ipsilateral trigeminal ganglion(TG)and brain stem(BS)tissue were sampled for molecular biological examination.Furthermore,by intrathecal injection of Nav1.3 antisense nucleotides or mismatch nucleotides in model animals and by local injection IL-6 or its antibody in sham surgical rats,the distribution of Nav1.3 was further investigated respectively.Results We found that the serum level of IL-1β,IL-6 and TNF-α in the TN group were significantly higher than that in the healthy group(p<0.05),and the IL-6 level was positively correlated with the severity of TN(r=0.989,p<0.05).The pain threshold began to decrease significantly at day 7 and reached the lowest point at day 14,postoperatively.The pathological examination showed local demyelinating of nerve in TN group.The WB and immunofluorescence results indicated that the expression of Nav1.3 and IL-6 in ION and TG in TN group was significantly higher than that in Sham group(p<0.05),while there was no significant difference in BS(p>0.05).Moreover,the Nav1.3 was co-expressed with IB4 and CGRP and the IL-6 was co-expressed with IB4,CGRP,NF200 and Nav1.3.The Nav1.3 expression changes were associated with local application of IL-6 and anti-IL-6(p<0.05).Conclusion The patients with trigeminal neuralgia have high serum levels of IL-1β,IL-2,IL-6,IL-8,TNF-α and IFN-γ,among which the IL-6 level is positively correlated with the severity of the disease.The Nav1.3 as well as IL-6 is highly expressed in nociceptive nerves of ether ION or TG.The expression of Nav1.3 is regulated by the IL-6.