Ebersberger A, Grubb B D, Willingale H L, Gardiner N J, Nebe J, Schaible H G
Physiologisches Institut der Universität Würzburg, Germany.
Neuroscience. 1999;93(2):775-81. doi: 10.1016/s0306-4522(99)00164-5.
In anaesthetized rats, the intraspinal release of immunoreactive prostaglandin E2 was measured using antibody microprobes. We addressed the question of whether the release of immunoreactive prostaglandin E2 is altered during development of acute inflammation in the knee evoked by intra-articular injections of kaolin and carrageenan. We also examined cyclo-oxygenase-1 and cyclo-oxygenase-2 protein levels in the spinal cord during the development of inflammation using the same model of arthritis. Densitometric analysis of microprobes showed that basal release of immunoreactive prostaglandin E2 in the period 175-310 min after kaolin was slightly higher than in the absence of inflammation. A pronounced enhancement of basal release of immunoreactive prostaglandin E2 was observed 430-530 min after kaolin. Enhanced levels of immunoreactive prostaglandin E2 were observed throughout the dorsal and ventral horns. Release of immunoreactive prostaglandin E2 was not altered further by the application of innocuous and noxious pressure onto the inflamed knee. Western blot analysis revealed that cyclo-oxygenase-2 but not cyclo-oxygenase-1 protein levels were elevated in the spinal cords of animals with inflammation compared to normal animals. This effect was evident as early as 3 h after the induction of arthritis. The maximum elevation of cyclo-oxygenase-2 protein levels (six-fold) was observed 12 h after the induction of arthritis. The results show that there is a tonic release of immunoreactive prostaglandin E2 from the spinal cord following the induction of arthritis, which is accompanied by enhanced expression of cyclo-oxygenase-2 protein in the spinal cord. We suggest that intraspinal prostaglandins may play a role in inflammation-evoked central sensitization of spinal cord neurons.
在麻醉大鼠中，使用抗体微探针测量脊髓内免疫反应性前列腺素E2的释放。我们研究了关节内注射高岭土和角叉菜胶诱发膝关节急性炎症过程中，免疫反应性前列腺素E2的释放是否发生改变。我们还使用相同的关节炎模型，检测了炎症发展过程中脊髓中环氧化酶-1和环氧化酶-2的蛋白水平。微探针的光密度分析显示，高岭土注射后175 - 310分钟期间，免疫反应性前列腺素E2的基础释放略高于无炎症时。高岭土注射后430 - 530分钟，观察到免疫反应性前列腺素E2的基础释放显著增强。在整个背角和腹角均观察到免疫反应性前列腺素E2水平升高。对发炎的膝关节施加无害和有害压力，并未进一步改变免疫反应性前列腺素E2的释放。蛋白质印迹分析显示，与正常动物相比，炎症动物脊髓中环氧化酶-2而非环氧化酶-1的蛋白水平升高。这种效应在关节炎诱导后3小时就很明显。关节炎诱导后12小时，观察到环氧化酶-2蛋白水平的最大升高（6倍）。结果表明，关节炎诱导后脊髓中存在免疫反应性前列腺素E2的持续性释放，同时伴有脊髓中环氧化酶-2蛋白表达增强。我们认为脊髓内前列腺素可能在炎症诱发的脊髓神经元中枢敏化中起作用。
