The role of Na(V)1.8 sodium channel in the maintenance of chronic inflammatory hypernociception.

We previously described an animal model of persistent inflammatory sensitization of nociceptors. In this model the hypernociception persists for more than 30 days after the cessation of 2 weeks of daily intraplantar treatment with prostaglandin E(2) (PGE(2)). The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel Na(V)1.8 is considered a characteristic of primary afferent nociceptive C fibers and plays an important role in acute hypernociception. In the present study, the relevance of the Na(V)1.8 channel was investigated in this model of persistent mechanical hypernociception in rats. In the PGE(2)-induced persistent hypernociception, but not in the single injection-induced acute hypernociception, the mRNA expression (RT-PCR) of Na(V)1.8 in dorsal root ganglia (DRG) was up-regulated. A similar increase of Na(V)1.8 mRNA was observed when DbcAMP was used to induce persistent hypernociception. Four daily intrathecal administrations of oligodeoxynucleotides (ODN) antisense against Na(V)1.8 decreased the mRNA encoding Na(V)1.8 in DRG. The intrathecal administration of ODN antisense prevented the PGE(2)-induced acute hypernociception and significantly reduced ongoing PGE(2)-induced persistent hypernociception. A parallel restoration of the persistent hypernociception and up-regulation of Na(V)1.8 mRNA was observed after the cessation of ODN antisense treatment. These results suggest the participation of Na(V)1.8 channels in the development and maintenance of chronic inflammatory hyperalgesia, and confirm their involvement in the acute inflammatory hypernociception.