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

• Published in: Current therapeutic research Vol. 70; no. 2; pp. 129 - 135
• Main Authors: Demirpence, Savas, Kurul, Semra Hiz, Kiray, Müge, Tugyan, Kazim, Yilmaz, Osman, Köse, Galip
• Format: Journal Article
• Language: English
• Published: New York, NY EM Inc USA 01.04.2009; Elsevier
• Subjects: adolescence; Biological and medical sciences; carrageenan; Internal Medicine; Medical Education; Medical sciences; migraine; Neurology; nitric oxide synthase; Pharmacology. Drug treatments; sumatriptan; Vascular diseases and vascular malformations of the nervous system; adolescence; migraine; nitric oxide synthase; carrageenan; sumatriptan; Agonist; Sumatriptan; Brain stem; Central nervous system; Cardiovascular disease; 5-HT1 Serotonine receptor; Biosynthesis; Serotonin agonist; Encephalon; Vascular disease; Randomization; Pain; Triptan derivatives; Cerebrovascular disease; Nervous system diseases; Iatrogenic; Enzyme; Antimigrainous agent; Migraine; Inflammation; Experimental study; Young animal; Nitric-oxide synthase; Cerebral disorder; Central nervous system disease; Oxidoreductases; Carrageenan
• ISSN: 0011-393X; 1879-0313
• DOI: 10.1016/j.curtheres.2009.04.003

Background: Migraine is a common disabling disorder of childhood and adolescence. Despite advances in the understanding of migraine pathophysiology, treatment remains a challenge. Objectives: 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.