Ambrosini Snijezanna S, Coderre Terence J
Department of Anesthesia, McGill University, Canada; Department of Psychology, McGill University, Canada.
Neurosci Lett. 2006 Dec 6;409(3):224-9. doi: 10.1016/j.neulet.2006.09.051. Epub 2006 Oct 6.
We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK) and protein kinase C (PKC), in a model of persistent pain using intrathecal (i.t.) (R,S)-3,5-dihydroxyphenylglycine (DHPG). Spontaneous nociceptive behaviours (SNBs), mechanical allodynia (von Frey thresholds) and heat hyperalgesia (plantar test latencies) induced by DHPG were measured in animals pretreated i.t. with membrane permeable inhibitors of ERK (PD 98059) and PKC (GF 109203X). Spinal administration of PD 98059 dose-dependently reduced SNBs, and attenuated both mechanical allodynia and heat hyperalgesia induced by DHPG. GF 109203X treatment also reduced SNBs and heat hyperalgesia, but did not affect mechanical allodynia induced by DHPG. Neither PD 98059, nor GF 109203X, altered mechanical or thermal thresholds in saline-injected control rats. These results suggest that both ERK and PKC are involved in persistent pain associated with the i.t. administration of DHPG.
我们使用鞘内注射（i.t.）（R，S）-3,5-二羟基苯甘氨酸（DHPG），在持续性疼痛模型中研究了两种细胞内第二信使，即细胞外信号调节蛋白激酶（ERK）和蛋白激酶C（PKC）的作用。在鞘内预先注射ERK膜通透抑制剂（PD 98059）和PKC膜通透抑制剂（GF 109203X）的动物中，测量由DHPG诱导的自发伤害性行为（SNB）、机械性异常性疼痛（von Frey阈值）和热痛觉过敏（足底试验潜伏期）。鞘内注射PD 98059剂量依赖性地减少了SNB，并减轻了由DHPG诱导的机械性异常性疼痛和热痛觉过敏。GF 109203X处理也减少了SNB和热痛觉过敏，但不影响由DHPG诱导的机械性异常性疼痛。PD 98059和GF 109203X均未改变注射生理盐水的对照大鼠的机械或热阈值。这些结果表明，ERK和PKC均参与与鞘内注射DHPG相关的持续性疼痛。
