Schaible H G, Neugebauer V, Geisslinger G, Beck U
Physiologisches Institut der Universität Würzburg, Röntgenring 9, D-97070 Würzburg, Germany.
Brain Res. 1998 Jul 6;798(1-2):287-93. doi: 10.1016/s0006-8993(98)00429-6.
Using antibody coated microprobes in anesthetized rats, we studied the intraspinal release of immunoreactive substance P during development of kaolin/carrageenan-induced inflammation in the knee joint, and the effects of S- and R-flurbiprofen on inflammation-evoked intraspinal release of immunoreactive substance P once inflammation was established. During the first 6 h after induction of acute inflammation, the basal release and the release of immunoreactive substance P evoked by innocuous pressure applied to the knee showed increases (n=4 rats). An intravenous dose of 9 mg/kg S-flurbiprofen (a potent inhibitor of cyclooxygenases that is anti-inflammatory and antinociceptive) did not significantly alter the pattern of inflammation-evoked release of immunoreactive substance P within 2 h although this dose reduced the responses of spinal cord neurons to pressure applied to the inflamed knee joint within 15 min to about 15% of the predrug value (Neugebauer et al., J. Pharmacol. Exp. Ther. 275 (1995) 618-628). The subsequent i.v. injection of 27 mg/kg S-flurbiprofen significantly changed the pattern of release of immunoreactive substance P showing a reduction of the level of immunoreactive substance P in the dorsal horn within 1 h (n=4 rats). The release of immunoreactive substance P was also reduced after the i.v. injection of 27 mg/kg R-flurbiprofen that is also antinociceptive but less anti-inflammatory (n=5 rats). These data show that both S- and R-flurbiprofen reduce the inflammation-evoked intraspinal release of immunoreactive substance P within hours. However, the reduction of release of immunoreactive substance P does not seem to be a prerequisite for the initial antinociceptive action of non-steroidal anti-inflammatory drugs. It may be rather important in the long term range.
我们在麻醉大鼠中使用抗体包被的微探针，研究了高岭土/角叉菜胶诱导的膝关节炎症发展过程中脊髓内免疫反应性P物质的释放，以及炎症建立后S-和R-氟比洛芬对炎症诱发的脊髓内免疫反应性P物质释放的影响。在急性炎症诱导后的最初6小时内，基础释放以及对膝关节施加无害压力所诱发的免疫反应性P物质的释放均增加（n = 4只大鼠）。静脉注射9 mg/kg的S-氟比洛芬（一种有效的环氧化酶抑制剂，具有抗炎和镇痛作用）在2小时内并未显著改变炎症诱发的免疫反应性P物质释放模式，尽管该剂量在15分钟内将脊髓神经元对发炎膝关节施加压力的反应降低至给药前值的约15%（Neugebauer等人，《药理学与实验治疗学杂志》275 (1995) 618 - 628）。随后静脉注射27 mg/kg的S-氟比洛芬显著改变了免疫反应性P物质的释放模式，在1小时内显示背角内免疫反应性P物质水平降低（n = 4只大鼠）。静脉注射27 mg/kg同样具有镇痛作用但抗炎作用较弱的R-氟比洛芬后，免疫反应性P物质的释放也减少了（n = 5只大鼠）。这些数据表明，S-和R-氟比洛芬在数小时内均能减少炎症诱发的脊髓内免疫反应性P物质的释放。然而，免疫反应性P物质释放的减少似乎并非非甾体抗炎药初始镇痛作用的先决条件。从长远来看，这可能相当重要。
