Buritova J, Honoré P, Besson J M
Physiopharmacologie du Système Nerveux, INSERM U161, Paris, France.
Brain Res. 1995 Mar 20;674(2):211-20. doi: 10.1016/0006-8993(95)00009-f.
This study evaluated the 'evoked' expression of Krox-24 protein in the lumbar spinal cord after peripheral carrageenan-induced inflammation and its modification by preadministration of indomethacin, a non-steroidal anti-inflammatory drug, in freely moving rats. Three h after intraplantar carrageenan (6 mg/150 microliters saline) a maximal 'evoked' Krox-24 expression was observed in L2-L6 segments of the dorsal horn ipsilateral to carrageenan inflammation. A maximal number of 'evoked' Krox-24 neurons was observed in L4-L5 segments, predominantly in the superficial laminae (I-II) and to a lesser extent in the medial part of neck (laminae V-VI) of the dorsal horn. Such an increase was not observed after an intraplantar injection of control vehicle saline. increase doses of carrageenan (1, 3 and 6 mg) induced a dose-dependent increase (r2 = 0.617, P < 0.0001) in the number of evoked' Krox-24 neurons observed in the superficial dorsal horn 3 h after carrageenan. Systemic preadministration of indomethacin (1, 2.5 and 5 mg/kg) dose-dependently reduced (r2 = 0.508, P < 0.0001) the total number of carrageenan (6 mg at 3 h)-'evoked' Krox-24 neurons (29 +/- 5, 45 +/- 4 and 57 +/- 2% reduction as compared with control, respectively). Systemic indomethacin dose-dependently reduced the inflamed paw and ankle diameter (16 +/- 8, 34 +/- 12, 54 +/- 6% and 48 +/- 14,. 75 + 16, 90 +/- 7% reduction as compared with the control carrageenan inflammation, respectively). There was a positive correlation between the effect of systemic indomethacin on both 'evoked' Krox-24 expression in superficial laminae and the inflammatory signs (r2 = 0.25, P < 0.01 for the paw diameter; r2 = 0.22, P < 0.05 for the ankle diameter). In addition, the total number of 'evoked' Krox-24 neurons was significantly reduced (43 +/- 5% reduction as compared with control) by an oral pretreatment of indomethacin (10 + 10 mg/kg). Oral indomethacin totally blocked the ankle diameter and reduced the paw diameter (100 + 14 and 30 +/- 6% reduction of the control carrageenan inflammation, respectively).
本研究评估了在自由活动的大鼠中，外周注射角叉菜胶诱导炎症后，腰椎脊髓中Krox-24蛋白的“诱导性”表达，以及非甾体抗炎药吲哚美辛预先给药对其的影响。足底注射角叉菜胶（6毫克/150微升生理盐水）3小时后，在角叉菜胶炎症同侧背角的L2-L6节段观察到最大的“诱导性”Krox-24表达。在L4-L5节段观察到最大数量的“诱导性”Krox-24神经元，主要位于背角的浅层层（I-II），在背角颈部内侧部分（V-VI层）的数量较少。足底注射对照溶媒生理盐水后未观察到这种增加。增加角叉菜胶剂量（1、3和6毫克）可诱导在角叉菜胶注射后3小时在浅背角观察到的“诱导性”Krox-24神经元数量呈剂量依赖性增加（r2 = 0.617，P < 0.0001）。吲哚美辛（1、2.5和5毫克/千克）全身预先给药剂量依赖性地减少了角叉菜胶（3小时时6毫克）“诱导性”Krox-24神经元的总数（与对照相比分别减少29±5%、45±4%和57±2%）。吲哚美辛全身给药剂量依赖性地减少了发炎爪和踝关节的直径（与对照角叉菜胶炎症相比分别减少16±8%、34±12%、54±6%和48±14%、75±16%、90±7%）。吲哚美辛对浅层层“诱导性”Krox-24表达和炎症体征的影响之间存在正相关（爪直径r2 = 0.25，P < 0.01；踝关节直径r2 = 0.22，P < 0.05）。此外，吲哚美辛（10 + 10毫克/千克）口服预处理显著减少了“诱导性”Krox-24神经元的总数（与对照相比减少43±5%）。口服吲哚美辛完全消除了踝关节直径并减少了爪直径（分别为对照角叉菜胶炎症的100±14%和30±6%）。
