title: The effect of sumatriptan on nitric oxide synthase enzyme production after iatrogenic inflammation in the brain stem of adolescent rats: A randomized, controlled, experimental study.
abstract: BACKGROUND
  Migraine is a common disabling disorder of childhood and adolescence. Despite advances in the understanding of migraine pathophysiology, treatment remains a challenge.
  
  
  OBJECTIVE
  The aims of this study were to investigate the production of nitric oxide synthase (NOS) enzymes in the brain stem of adolescent rats, using an experimental model of migraine, and the effect of sumatriptan pretreatment on the production of the NOS enzymes.
  
  
  METHODS
  Male adolescent (aged ~2 months) Wistar rats were used in the study. The animals were anesthetized using pentobarbital. The trigeminovascular system was stimulated by injecting a proinflammatory molecule, carrageenan, into the cis-terna magna of the anesthetized rats. The animals were divided into 3 groups of equal size: (1) the study group, in which the rats were treated with sumatriptan succinate 2 hours before intracisternal carrageenan injection; (2) the sham group, in which the rats were not administered intracisternal carrageenan injection or sumatriptan pretreatment; and (3) the control group, in which the rats were administered intracisternal carrageenan injection but were not pretreated with sumatriptan. In the control and study groups, the rats were euthanized using ether anesthesia 1 hour after intracisternal carrageenan injection. Rats in the sham group were euthanized 1 hour after intracisternal catheterization. Brain tissue was removed and endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) immunohistochemistry was performed.
  
  
  RESULTS
  Twenty-one rats were randomized into 3 groups of 7. The mean values of the immunolabeling intensities for eNOS, nNOS, and iNOS enzymes in the brain stem were significantly lower in the sham group compared with the control group (P = 0.001, P = 0.002, and P = 0.001, respectively). The mean values of the immunolabeling intensities of eNOS, nNOS, and iNOS in the brain stem were significantly lower in the study group compared with the control group (P = 0.001, P = 0.025, and P = 0.005, respectively).
  
  
  CONCLUSIONS
  In this experimental model of migraine in adolescent rats, intracisternal injection of carrageenan was associated with a significant increase in the production of NOS enzymes in the brain stem. Pretreatment with sumatriptan was associated with a decrease in NOS production.
authors.affiliation: Department of Pediatrics, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Savas
authors.initials: S
authors.lastname: Demirpence
authors.affiliation: Department of Pediatrics, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Semra Hiz
authors.initials: SH
authors.lastname: Kurul
authors.affiliation: Department of Histology-Embryology, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Kiray
authors.affiliation: Department of Histology-Embryology, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Tugyan
authors.affiliation: Department of Laboratory Animal Sciences, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.affiliation: Department of Pediatrics, Dokuz Eylül University School of Medicine, Izmir, Turkey.
authors.forename: Galip
authors.initials: G
authors.lastname: Köse
keywords: adolescence; carrageenan; migraine; nitric oxide synthase; sumatriptan