Nav1.9 Channel Contributes to Mechanical and Heat Pain Hypersensitivity Induced by Subacute and Chronic Inflammation

摘要: Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading spontaneous pain and invalidating hypersensitivity. Given its role in regulating neuronal excitability, voltage-gated Nav1.9 channel a potential target treatment pathological pain, but implication inflammatory yet not fully described. In present study, we examined acute, subacute chronic using Nav1.9-null mice knock-down rats. found that, although does contribute basal thresholds, it plays an important heat hypersensitivity induced by paw inflammation (intraplantar carrageenan) ankle (complete Freund's adjuvant-induced monoarthritis). We showed first time that also contributes mechanical both models, as assessed von Frey dynamic weight bearing tests. Consistently, antisense-based gene silencing rats reduced carrageenan-induced While no changes mRNA levels were detected dorsal root ganglia (DRGs) during inflammation, significant increase immunoreactivity was observed ipsilateral DRGs 24 hours following carrageenan injection. This correlated with immunolabeling nerve fibers surrounding inflamed area. No change current density could soma retrolabeled DRG neurons innervating tissues, suggesting newly produced channels may non-functional at this level rather axonal transport. Our results provide evidence crucial generation hypersensitivity, bring new elements understanding regulation those models.