Gould Harry J, England John D, Soignier R Denis, Nolan Porter, Minor Lerna D, Liu Z P, Levinson S Rock, Paul Dennis
Department of Neurology, Louisiana State University Health Sciences Center, 533 Bolivar Street, Room 325, New Orleans, LA 70112, USA.
J Pain. 2004 Jun;5(5):270-80. doi: 10.1016/j.jpain.2004.04.005.
Although nerve growth factor plays a role in augmenting sodium channel expression in small dorsal root ganglion (DRG) cells, the cytochemical mediators responsible for enhanced expression in large DRG neurons are unknown. To narrow the search for mediators involved in the increased production of sodium channels in large DRG neurons, we examined the effect of cyclooxygenase inhibition on sodium channel production during inflammation. Thirty minutes before the subcutaneous injection of complete Freund's adjuvant (CFA), rats received ibuprofen (nonselective, cyclooxygenase inhibitor), NS-398 (selective, cyclooxygenase inhibitor), or vehicle. Withdrawal thresholds from thermal and mechanical stimulation were measured before and immediately after CFA injection and at selected hourly intervals after injection for the next 24 hours. Sodium channel up-regulation was then examined in DRG by using site-specific, anti-sodium channel antibodies, Na(v) 1.7 and 1.8. Both ibuprofen and NS-398 provided analgesia during the second phase of inflammatory hyperalgesia that begins 3 hours after CFA injection. The up-regulation, predominantly of Na(v) 1.7 and minimally of Na(v) 1.8 channels, seen in vehicle-treated rats was suppressed by both drugs at 24 hours after injection. By 72 hours after injection, no difference in labeling between the drug- and vehicle-treated animals was observed. Sodium channel labeling in large DRG neurons returned to baseline between 1 and 2 weeks after CFA injection, whereas small cell labeling persisted. The cytochemical signal for sodium channel up-regulation in the large DRG cells that most closely correlates with inflammatory hyperalgesia is mediated at least in part through products of the cyclooxygenase pathway.
Expression of sodium channels in dorsal root ganglia increases dramatically during inflammation. The increase in sodium channels is thought to enhance neuronal excitability and to play a role in hyperalgesia and wound vigilance during healing. We provide evidence that prostaglandins play a role in signaling channel augmentation.
尽管神经生长因子在增强小背根神经节（DRG）细胞中钠通道表达方面发挥作用，但负责大DRG神经元中钠通道表达增强的细胞化学介质尚不清楚。为了缩小对参与大DRG神经元中钠通道产量增加的介质的搜索范围，我们研究了环氧化酶抑制在炎症过程中对钠通道产生的影响。在皮下注射完全弗氏佐剂（CFA）前30分钟，大鼠接受布洛芬（非选择性环氧化酶抑制剂）、NS-398（选择性环氧化酶抑制剂）或赋形剂。在CFA注射前和注射后立即以及注射后接下来的24小时内每隔一小时测量热刺激和机械刺激的撤药阈值。然后使用位点特异性抗钠通道抗体Na(v) 1.7和1.8在DRG中检查钠通道上调情况。布洛芬和NS-398在CFA注射后3小时开始的炎症性痛觉过敏的第二阶段均提供镇痛作用。在注射后24小时，两种药物均抑制了在接受赋形剂处理的大鼠中观察到的主要为Na(v) 1.7通道且最少为Na(v) 1.8通道的上调。到注射后72小时，在接受药物处理和接受赋形剂处理的动物之间未观察到标记差异。CFA注射后1至2周内，大DRG神经元中的钠通道标记恢复到基线水平，而小细胞标记持续存在。与炎症性痛觉过敏最密切相关的大DRG细胞中钠通道上调的细胞化学信号至少部分是通过环氧化酶途径的产物介导的。
在炎症过程中，背根神经节中钠通道的表达会显著增加。钠通道的增加被认为会增强神经元兴奋性，并在愈合过程中的痛觉过敏和伤口警觉中发挥作用。我们提供证据表明前列腺素在信号传导通道增强中起作用。
