The role of Na_V1.8 sodium channel in the maintenance of chronic inflammatory hypernociception

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• 作者：Cristiane Flora Villarreal ; Daniela Sachs ; Fernando de Queiroz Cunha ; Carlos Amí ; lcar Parada and Sé ; rgio Henrique Ferreira
• 刊名：Neuroscience Letters
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：386
• 期：2
• 页码：72-77
• 全文大小：217 K

文摘

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 Na_V1.8 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_V1.8 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 Na_V1.8 in dorsal root ganglia (DRG) was up-regulated. A similar increase of Na_V1.8 mRNA was observed when DbcAMP was used to induce persistent hypernociception. Four daily intrathecal administrations of oligodeoxynucleotides (ODN) antisense against Na_V1.8 decreased the mRNA encoding Na_V1.8 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 Na_V1.8 mRNA was observed after the cessation of ODN antisense treatment. These results suggest the participation of Na_V1.8 channels in the development and maintenance of chronic inflammatory hyperalgesia, and confirm their involvement in the acute inflammatory hypernociception.