Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Mediators Inflamm. 2017;2017:2786427. doi: 10.1155/2017/2786427. Epub 2017 Aug 2.
Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 g/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.
瞬时受体电位香草酸亚型 1（TRPV1）是一种非选择性阳离子通道，主要表达于感觉神经元。TRPV1 在炎症性和神经性疼痛状态的发病机制中起着重要作用。先前的研究表明肿瘤坏死因子-α（TNF-α）与 TRPV1 之间存在相互作用，导致感觉神经元中离子通道功能和蛋白表达的调节。我们使用von Frey 和热板行为测试检查鞘内给予超强 TRPV1 激动剂树脂毒素（RTX）对 TNF 诱导的大鼠疼痛相关行为的影响。鞘内注射 TNF 后 24 小时诱导机械性痛觉过敏（2 和 20ng/kg）和热痛觉过敏（200ng）。RTX（1.9μg/kg）的额外鞘内给药可减轻 TNF 诱导的机械性痛觉过敏和热痛觉过敏，在注射后 24 小时。此外，TNF 增加 TRPV1 蛋白水平和 TRPV1 表达神经元的数量。这两种作用都可以通过 RTX 的给药来消除。这些结果表明，TRPV1 参与 TNF 诱导的疼痛为 TNF 诱导的疼痛提供了新的 TRPV1 为基础的实验治疗方法，并证明了 RTX 在炎症性疼痛疾病中的镇痛潜力。
