Sammons M J, Raval P, Davey P T, Rogers D, Parsons A A, Bingham S
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, UK.
Brain Res. 2000 Sep 8;876(1-2):48-54. doi: 10.1016/s0006-8993(00)02596-8.
NGF is an important link between inflammation and hyperalgesia and interacts with many different mediators of inflammation, including the MAPK signaling pathway. In these studies, carrageenan-induced thermal hyperalgesia was evaluated in the mouse and the role of NGF and the MAPK pathway investigated. Carrageenan induced a time-dependent inflammation and thermal hyperalgesia, which was maximal 4 h post administration. Both indomethacin (0.3, 1.0 and 10 mg/kg s.c., 30 min pre-carrageenan) and morphine (0.4, 1.2, 4.0 mg/kg; s.c., 30 min pre-hyperalgesia measurement) significantly inhibited carrageenan-induced thermal hyperalgesia and indomethicin inhibited paw inflammation, demonstrating the model as suitable for the assessment of anti-hyperalgesic and anti-inflammatory agents. Anti-NGF (0.67 mg/kg sc, 60 min pre-carrageenan) produced a significant inhibition of thermal hyperalgesia, but not inflammation. NGF itself produced a time-dependent hyperalgesia, but not inflammation, following intraplantar injection. The specific MAPK pathway inhibitor, PD98059 (0.1, 0.3 and 1 mg/kg sc, 30 min pre-carrageenan) significantly inhibited carrageenan-induced hyperalgesia, but not inflammation. These data demonstrate a role for both NGF and the MAPK signaling pathway in the production of thermal hyperalgesia, but not inflammation, in the mouse.
神经生长因子（NGF）是炎症与痛觉过敏之间的重要联系，并且与许多不同的炎症介质相互作用，包括丝裂原活化蛋白激酶（MAPK）信号通路。在这些研究中，在小鼠身上评估了角叉菜胶诱导的热痛觉过敏，并研究了NGF和MAPK通路的作用。角叉菜胶诱导了时间依赖性的炎症和热痛觉过敏，在给药后4小时达到最大值。吲哚美辛（0.3、1.0和10mg/kg皮下注射，在角叉菜胶注射前30分钟）和吗啡（0.4、1.2、4.0mg/kg；皮下注射，在痛觉过敏测量前30分钟）均显著抑制角叉菜胶诱导的热痛觉过敏，且吲哚美辛抑制爪部炎症，这表明该模型适用于评估抗痛觉过敏和抗炎药物。抗NGF（0.67mg/kg皮下注射，在角叉菜胶注射前60分钟）显著抑制热痛觉过敏，但不抑制炎症。足底注射NGF本身会产生时间依赖性的痛觉过敏，但不引起炎症。特异性MAPK通路抑制剂PD98059（0.1、0.3和1mg/kg皮下注射，在角叉菜胶注射前30分钟）显著抑制角叉菜胶诱导的痛觉过敏，但不抑制炎症。这些数据表明，在小鼠热痛觉过敏而非炎症的产生过程中，NGF和MAPK信号通路均发挥了作用。
