Maihöfner C, Tegeder I, Euchenhofer C, deWitt D, Brune K, Bang R, Neuhuber W, Geisslinger G
Institut für Experimentelle Pharmakologie and Toxikologie, Universität Erlangen, Universitätsstr. 22, 91054, Erlangen, Germany.
Neuroscience. 2000;101(4):1093-108. doi: 10.1016/s0306-4522(00)00361-4.
Prostaglandins are important mediators in spinal nociceptive processing. They are produced by cyclo-oxygenase isoforms, cyclo-oxygenase-1 and -2, which are both constitutively expressed in the central nervous system. The present immunohistochemical study details localization and regulation of cyclo-oxygenase-1 and -2 and neuronal nitric oxide synthase in lumbar spinal cord before and after induction of a painful paw inflammation in mice. Cyclo-oxygenase-1 immunoreactivity was found in glial cells of the dorsal and ventral horns, but not in neurons. In unstimulated mice, cyclo-oxygenase-2 immunoreactivity was found in motoneurons of the ventral horns and in lamina X, but not in dorsal horn neurons. After induction of a paw inflammation with zymosan, cyclo-oxygenase-2 immunoreactivity increased dramatically in dorsal horn neurons of laminae I-VI and X, paralleled by a significant increase in prostaglandin E(2) release from lumbar spinal cord. Cyclo-oxygenase-2 was co-localized with neuronal nitric oxide synthase immunoreactivity in several neurons in superficial laminae of the dorsal horns and in the area surrounding the central canal. Nitric oxide synthase was distributed in the cytoplasm and extended to processes of some neurons. In contrast, electron microscopy revealed that cyclo-oxygenase-2 immunoreactivity was restricted to the nuclear membrane and rough endoplasmic reticulum. It is shown in the present study that both cyclo-oxygenase isoforms are constitutively expressed in the spinal cord, cyclo-oxygenase-1 in glial cells of the dorsal and ventral horns and cyclo-oxygenase-2 in motoneurons. After induction of a hindpaw inflammation, several dorsal horn neurons express cyclo-oxygenase-2. Some of them are also positive for neuronal nitric oxide synthase, which is also induced following peripheral inflammation. Intracellularly, cyclo-oxygenase-2 is bound to the membranes of the nucleus and endoplasmic reticulum, whereas neuronal nitric oxide synthase is found in the cytoplasm.
前列腺素是脊髓伤害性感受处理过程中的重要介质。它们由环氧化酶同工型，即环氧化酶-1和-2产生，这两种酶在中枢神经系统中均组成性表达。本免疫组织化学研究详细阐述了在小鼠爪部诱发疼痛性炎症前后，腰脊髓中环氧化酶-1和-2以及神经元型一氧化氮合酶的定位和调节情况。在背角和腹角的胶质细胞中发现了环氧化酶-1免疫反应性，但在神经元中未发现。在未受刺激的小鼠中，腹角运动神经元和X层中发现了环氧化酶-2免疫反应性，但在背角神经元中未发现。用酵母聚糖诱发爪部炎症后，I-VI层和X层背角神经元中的环氧化酶-2免疫反应性显著增加，同时腰脊髓中前列腺素E(2)的释放也显著增加。环氧化酶-2与神经元型一氧化氮合酶免疫反应性在背角浅层的几个神经元以及中央管周围区域共定位。一氧化氮合酶分布在细胞质中，并延伸到一些神经元的突起。相比之下，电子显微镜显示环氧化酶-2免疫反应性局限于核膜和粗面内质网。本研究表明，两种环氧化酶同工型在脊髓中均组成性表达，环氧化酶-1在背角和腹角的胶质细胞中表达，环氧化酶-2在运动神经元中表达。诱发后爪炎症后，几个背角神经元表达环氧化酶-2。其中一些神经元对神经元型一氧化氮合酶也呈阳性，该酶在周围炎症后也被诱导。在细胞内，环氧化酶-2与细胞核和内质网的膜结合，而神经元型一氧化氮合酶存在于细胞质中。
