Localization and regulation of cyclo-oxygenase-1 and-2 and neuronal nitricoxide synthase in mouse spinal cord

Prostaglandins are important mediators in spinal nociceptive processing. Th ey are produced by cyclo-oxygenase isoforms, cyclo-oxygenase-1 and -2, whic h are both constitutively expressed in the central nervous system. The pres ent 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-ox ygenase-1 immunoreactivity was found in glial cells of the dorsal and ventr al horns, but not in neurons. In unstimulated mice, cyclo-oxygenase-2 immun oreactivity 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 dorsa l 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 sever al neurons in superficial laminae of the dorsal horns and in the area surro unding the central canal. Nitric oxide synthase was distributed in the cyto plasm and extended to processes of some neurons. In contrast, electron micr oscopy revealed that cyclo-oxygenase-2 immunoreactivity was restricted to t he nuclear membrane and rough endoplasmic reticulum. It is shown in the present study that both cyclo-oxygenase isoforms are con stitutively expressed in the spinal cord, cyclooxygenase-1 in glial cells o f the dorsal and ventral horns and cyclo-oxygenase-2 in motoneurons. After induction of a hindpaw inflammation, several dorsal horn neurons express cy clo-oxygenase-2. Some of them are also positive for neuronal nitric oxide s ynthase, which is also induced following peripheral inflammation Intracellu larly, cyclo-oxygenase-2 is bound to the membranes of the nucleus and endop lasmic reticulum, whereas neuronal nitric oxide synthase is found in the cy toplasm. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reser ved.