Elsevier

Neuroscience Letters

Volume 386, Issue 2, 30 September 2005, Pages 72-77
Neuroscience Letters

The role of NaV1.8 sodium channel in the maintenance of chronic inflammatory hypernociception

https://doi.org/10.1016/j.neulet.2005.04.060Get rights and content

Abstract

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 E2 (PGE2). The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel NaV1.8 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 NaV1.8 channel was investigated in this model of persistent mechanical hypernociception in rats. In the PGE2-induced persistent hypernociception, but not in the single injection-induced acute hypernociception, the mRNA expression (RT-PCR) of NaV1.8 in dorsal root ganglia (DRG) was up-regulated. A similar increase of NaV1.8 mRNA was observed when DbcAMP was used to induce persistent hypernociception. Four daily intrathecal administrations of oligodeoxynucleotides (ODN) antisense against NaV1.8 decreased the mRNA encoding NaV1.8 in DRG. The intrathecal administration of ODN antisense prevented the PGE2-induced acute hypernociception and significantly reduced ongoing PGE2-induced persistent hypernociception. A parallel restoration of the persistent hypernociception and up-regulation of NaV1.8 mRNA was observed after the cessation of ODN antisense treatment. These results suggest the participation of NaV1.8 channels in the development and maintenance of chronic inflammatory hyperalgesia, and confirm their involvement in the acute inflammatory hypernociception.

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Acknowledgements

The authors thank Ieda R. Schiavo for technical support. This work was supported by FAPESP, São Paulo, Brazil.

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