Investigation of the immunoreactivities of nitric oxide synthase enzymes and the effect of sumatriptan and topiramate in adolescent rats using an experimental model of migraine

Objective: The aim of this study was to investigate the immunoreactivities for nitric oxide synthase enzymes in the brains of the adolescent rats using an experimental model of migraine and the effect of sumatriptan and topiramate pre-treatments on the immunoreactivities of the nitric oxide synthase enzymes.Material and Methods: Male adolescent Wistar rats (66-115g) were used. The stimulation of the trigeminovascular system was induced by injecting a pro-inflammatory molecule, carrageenan, into the cisterna magna of the anaesthetized rats. In the sumatriptan and topiramate groups, the rats were divided into 3 subgroups: Group 1 rats did not taken intracisternal carrageenan injection nor antimigraine pretreatment. Group 2 rats were taken intracisternal carrageenan injection, but did not taken antimigraine pretreatment. Group 3 rats were treated with sumatriptan succinate 2 hours before intracisternal carrageenan injection in sumatriptan group and with topiramate throughout four weeks before intracisternal carrageenan injection in topiramate group. Rats were sacrificed at one hour after intracisternal carrageenan injection. Brain tissues were removed and eNOS, nNOS and iNOS immunohistochemistry was performed. The mean values of the three subgroups were compared to each other both in sumatriptan and topiramate groups.Results: In sumatriptan and topiramate groups, the mean values of immunolabeling intensities for eNOS, nNOS and iNOS in brain stem and frontal cortex of the rats were significantly increased in group 2 compared to group 1. In sumatriptan group, the mean values of immunolabeling intensities for eNOS, nNOS and iNOS in brain stem and nNOS in frontal cortex of the rats were significantly decreased in group 3 compared to group 2. In topiramate group, the mean values of immunolabeling intensities for nNOS and iNOS in brain stem and eNOS and nNOS in frontal cortex of the rats were significantly decreased in group 3 compared to group 2Conclusion: These findings suggest that, intracisternal injection of carrageenan caused a significant increase in the immunoreactivities of NOS enzymes in brains of adolescent rats. The increased NOS immunoreactivities could be antagonized by pre-treatment with sumatriptan and topiramate. These data may allow in the future to try new therapeutic strategies for NOS inhibitors in order to alleviate migraine headache.Key words: migraine, adolescence, carrageenan, nitric oxide, nitric oxide synthetase, sumatriptan, topiramate