Localization and regulation of cyclo-oxygenase-1 and -2 and neuronal nitric oxide synthase in mouse spinal cord
Section snippets
Animals
Experiments were performed using male C57 black/6 mice (18–20 g, Charles River, Sulzfeld, Germany). The animals had free access to food and water. They were maintained in climate- and light-controlled rooms (24±0.5°C, 12 h/12 h dark–light cycle). The study was approved by the local Ethics Committee for animal research, and the guidelines set out by the International Association for the study of pain were obeyed in all experiments. All efforts were made to minimize both the suffering and the number
Spontaneous pain
After the intraplantar injection of 2.5 mg zymosan, mice showed an immediate and intense behavioral response that lasted for up to 30–45 min, and generally consisted of licking, biting and spontaneous flicking of the paw.
Paw edema
Intraplantar zymosan produced an increase in paw thickness. One hundred and sixty-eight hours after zymosan injection into the right hindpaw mice showed a 2.5-fold increase in the right paw volume (0.3±0.05 ml; mean±S.D.) compared to pretreatment values (0.12±0.02 ml), whereas paw
Discussion
The present data confirm and extend the current conception of the localization and regulation of the cyclo-oxygenase isoforms in the spinal cord. In addition to the previously described constitutive expression of both cyclo-oxygenase isoforms in rat spinal cord and up-regulation of cyclo-oxygenase-2 mRNA,5., 21. we could demonstrate (i) that cyclo-oxygenase-1 immunoreactivity in the mouse spinal cord is found exclusively in glial cells of the dorsal and ventral horns, (ii) that there is no
Conclusions
We report the distribution and regulation of cyclo-oxygenase-1-, cyclo-oxygenase-2- and nNOS-immunoreactive cells in the spinal cord in a model of a painful peripheral inflammation in mice. We show that cyclo-oxygenase-1 and -2 are both constitutively expressed in the spinal cord, cyclo-oxygenase-1 in glial cells of the dorsal and ventral horns, and cyclo-oxygenase-2 in motoneurons and astrocytes. Peripheral inflammation results in a dramatic increase in cyclo-oxygenase-2 immunoreactivity in
Acknowledgements
This study was supported by the Deutsche Forschungsgemeinschaft (SFB 553 and SFB 353). We would like to thank Beate Layh, Doris Schreiner, Claudia Labahn and Tanja Mittmann for excellent technical assistance. We are grateful to Dr Bernd Mayer for kindly providing the antibody against nNOS and to Andrea Hilpert for her support with the electron microscopy.
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