Villarreal Cristiane Flora, Sachs Daniela, Cunha Fernando de Queiroz, Parada Carlos Amílcar, Ferreira Sérgio Henrique
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo,14049-900 São Paulo, Brazil.
Neurosci Lett. 2005 Sep 30;386(2):72-7. doi: 10.1016/j.neulet.2005.04.060.
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.
我们之前描述过一种伤害感受器持续性炎性致敏的动物模型。在该模型中，每日足底注射前列腺素E2（PGE2）两周后停止注射，痛觉过敏仍持续超过30天。河豚毒素耐受（TTX-R）电压门控钠通道Na(V)1.8被认为是初级传入伤害性C纤维的一个特征，并且在急性痛觉过敏中起重要作用。在本研究中，我们在该大鼠持续性机械性痛觉过敏模型中研究了Na(V)1.8通道的相关性。在PGE2诱导的持续性痛觉过敏中，而非单次注射诱导的急性痛觉过敏中，背根神经节（DRG）中Na(V)1.8的mRNA表达（RT-PCR）上调。当使用二丁酰环磷腺苷（DbcAMP）诱导持续性痛觉过敏时，观察到Na(V)1.8 mRNA有类似的增加。每日鞘内注射四次针对Na(V)1.8的反义寡脱氧核苷酸（ODN）可降低DRG中编码Na(V)1.8的mRNA。鞘内注射ODN反义寡核苷酸可预防PGE2诱导的急性痛觉过敏，并显著减轻正在进行的PGE2诱导的持续性痛觉过敏。在停止ODN反义治疗后，观察到持续性痛觉过敏与Na(V)1.8 mRNA上调同时恢复。这些结果表明Na(V)1.8通道参与慢性炎性痛觉过敏的发生和维持，并证实它们参与急性炎性痛觉过敏。
