IL-6 contributes to Na_v1.3 up-regulation in trigeminal nerve following chronic constriction injury

Abstract

<b>Background</b>: To verify the hypothesis that the nature of trigeminal neuralgia (TN) is an ectopic impulse induced by sodium channel modulated by cytokines, we conducted an animal study using the infraorbital nerve chronic constriction injury (CCI) model in rats.<b>Method</b>: The expression of Nav1.3 or IL-6 in the infraorbital nerve (ION) and trigeminal ganglion (TG) were detected by western blot and immunocytochemistry after administration of antisense oligodeoxynucleotide sequence (AS), IL-6 or Anti-IL-6.<b>Results</b>: With intrathecal administration of AS or mismatch oligodeoxynucleotide sequence (MM) in the CCI rats, the Nav1.3-IR in ION and TG accounted for 2.2 ± 0.51% and 8.5 ± 3.1% in <i>AS+CCI</i> group <i>vs</i>. 6.9 ± 1.3% and 38.7 ± 4.8% in <i>MM+CCI</i> group (<i>p</i> < 0.05), respectively. While with local administration of IL-6 in those with sham operation, it accounted for 7.4 ± 2.1% and 45.5 ± 3.4% in <i>IL-6+ sham </i>group <i>vs. </i>1.9 ± 0.67% and 8.1 ± 1.3% in <i>vehicle+sham </i>group (<i>p</i> < 0.05); with local administration of anti-IL-6 in CCI rats, 4.5 ± 0.78% and 32.1 ± 9.6% in <i>Anti-IL-6+ CCI</i> group <i>vs</i> 8.9 ± 2.1% and 61.4 ± 11.2% in <i>vehicle+CCI </i>group (<i>p</i> < 0.05).<b>Discussion</b>: We believe that the emergence of Na_v1.3 from the compressed trigeminal nerve might be an important structural basis for the development of the ectopic excitability on the axon and IL-6 may play a role of necessary precondition.