The Effects of Topiramate and Flunarizine on serum Glutamine and neuropeptide Y levels in adolescent Rats with a Migraine model
Abstract
This study aimed to investigate the effects of topiramate and flunarizine on serum glutamine and neuropeptide Y (NPY) levels in adolescent (6 weeks) rats with a migraine model induced by trinitroglycerin (NTG). For this purpose, 48 Wistar albino male rats in the adolescent stage were used. The rats were divided into 6 groups, each consisting of 8 animals. Group 1 (n=8): Healthy control group; no agent was applied. Group 2 (n=8): Migraine group; NTG (10 mg/kg, IP) was administered once daily. Group 3 (n=8): Migraine + Topiramate group; NTG (10 mg/ kg, IP) was administered once daily, and topiramate (50 mg) was administered orally twice a day. Group 4 (n=8): Migraine + Flunarizine group; NTG (10 mg/kg, IP) was administered once daily, and flunarizine (5 mg) was administered orally twice a day. Group 5 (n=8): Topiramate group only; topiramate (50 mg) was administered orally twice a day. Group 6 (n=8): Flunarizine group only; flunarizine (5 mg) was administered orally twice a day. All applications were performed for 5 days. In the migraine-induced group, a significant increase in glutamine and NPY levels was observed compared to the control group. However, in the topiramate and flunarizine groups (grup 5 and 6), no significant differences were detected in these levels compared to the control group. The NTG application was found to be suitable for creating a migraine model, but to observe better clinical findings, an increase in both dose and duration may be necessary. It was concluded that migraine results in brain damage, and as an indicator of damage, both NPY and glutaminase levels may increase. Glutaminase might be slightly more sensitive than NPY in detecting brain damage in migraine, but this sensitivity should be further compared in more experimental studies.
Downloads
References
Graves BW. Management of migraine headaches. J. Midwifery Womens Health. [Internet]. 2006; 51(3):174–184. doi: https://doi.org/bxs453
Serdaroğlu, E. Evaluation of Occipital Region Headache in Children: Descriptive Research. Turk. Klin. J. Pediatr. [Internet]. 2022; 31(1):53-58. doi: https://doi.org/pwwn
Bektaş G. Pediatrik Migrenin Önleyici Tedavisi: Amitriptilin mi Topiramat mı? Turk. J. Neurol. [Internet]. 2017; 23:90-91. doi: https://doi.org/pwwp
Kipoğlu O, Kırık S. Headache and Autoimmune Diseases. . In: Canpolat M, editor. Turkiye Klinikleri Pediatric Neurology - Special Topics Book Identity. Turk. Klin. [Internet]Ankara: Türkiye Clinics. 2023; p. 119-124.
Aydın H, Bucak İ. Çocuk nöroloji polikliniğine başvuran migren tanılı hastaların retrospektif özelliklerinin incelenmesi. Pamukkale Med. J. [Internet]. 2021; 14(2):330-336. doi: https://doi.org/pwwq
Kaya MZ, Pehlivan SB, Öner L. Migren Araştırmalarında Kullanılan Güncel Hayvan Modelleri. Hacet. J. Fac. Pharm. [Internet]. 2023; 43(4):364-379. doi: https://doi.org/pwwr
Koşal V, Okulmuş Ç, Koçak Y, Keleş ÖF, Ceylan N, Başbuğan Y. The Effect of Nitroglycerin in Testicular Histopathology, Reproductive Hormones and Testicular Oxidative Stress in Adolescent Rats. Mansoura Vet. Med. J. [Internet]. 2023; 24(3):12. doi: https://doi.org/pwws
Costa A, Smeraldi A, Tassorelli C, Greco R, Nappi G. Effects of acute and chronic restraint stress on nitroglycerin- induced hyperalgesia in rats. Neurosci. Lett. [Internet]. 2005; 383(1-2):7-11. doi: https://doi.org/dq47g4
Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A. Characterization of a novel model of chronic migraine. Pain. [Internet]. 2014; 155(2):269-274. doi: https://doi.org/f5pb7p
Uysal N, Gönenç S, Sönmez A, Aksu İ, Topçu A, Kayatekin BM, Açıkgöz O. Adölesan Sıçan Beyninde Antioksidan Enzim Aktiviteleri ve Lipid Peroksidasyon Düzeyleri. Ege. J. Med. [Internet]. 2005 [cited 2025 april 14]; 44(2):75-Available in: https://goo.su/XtMq
Ferrari A, Spaccalopelo L, Pinetti D, Tacchi R, Bertolini Effective prophylactic treatments of migraine lower plasma glutamate levels. Cephalalgia. [Internet]. 2009; 29(4):423-429. doi: https://doi.org/ddm2m2
Ahmi ÖZ, Uğuz AC. Migren patogenezinde oksidatif strese duyarlı TRP kanallarının rolleri. Med. J. SDÜ. [Internet]. 2015[cited 2025 april 14]; 22(4):144-150. Available in: https://goo.su/iSWg
Sufka KJ, Staszko SM, Johnson AP, Davis ME, Davis RE, Smitherman TA Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats. J. Headache Pain. [Internet]. 2016; 17:40. doi: https://doi.org/pwwt
Vanmolkot KR, Kors EE, Turk U, Turkdogan D, Keyser A, Broos LA, Kia SK, van den Heuvel JJ, Black DF, Haan J, Frants RR, Barone V, Ferrari MD, Casari G, Koenderink JB, van den Maagdenberg AM. Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure familial hemiplegic migraine. Eur. J. Hum. Genet. [Internet]. 2006; 14:555-560. doi: https://doi.org/b88zrw
Parpura V, Heneka MT, Montana V, Oliet SHR, Schousboe A, Haydon PG, Stout Jr RF, Spray DC, Reichenbach A, Pannicke T, Pekny M, Pekna M, Zorec R, Verkhratsky A. Glial cells in (patho)physiology. J. Neurochem. [Internet]. 2012; 121(1):4–27. doi: https://doi.org/fxpwcv
Boran HE, Bolay H. Pathophysiology of Migraine. Noro Psikiyatr Ars. [Internet]. 2013; 50:1-7. doi: https://doi.org/g34zv8
Hanani M, Verkhratsky A. Satellite Glial Cells and Astrocytes, a Comparative Review. Neurochem. Res. [Internet]. 2021; 46:2525–2537. doi: https://doi.org/ghzr43
Chen QW, Meng RT, Ko CY. Exploring Migraine Pathogenesis: Transcriptomic Insights and Pathway Analysis in Nitroglycerin-Induced Rat Model. Curr. Issues Mol. Biol. [Internet]. 2025; 47(4):241. doi: https://doi.org/pwwv
Colombo B, Dalla Libera D, Comi G: Brain white matter lesions in migraine: what’s the meaning? Neurol. Sci. [Internet]. 2011; 32(1):37-40. doi: https://doi.org/d8ktgj
Granziera C, Daducci A, Romascano D, Roche A, Helms G, Krueger G, Hadjikhani N: Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3T. Hum. Brain Mapp. [Internet]. 2014; 35:1461- 1468. doi: https://doi.org/f3nbkv
Granziera C, Romascano D, Daducci A, Roche A, Vincent M, Krueger G, Hadjikhani N: Migraineurs without aura show microstructural abnormalities in the cerebellum and frontal lobe. Cerebellum. [Internet]. 2013; 12:812– 818. doi: https://doi.org/gf8p7f
Coppola G, Casillo F, Sebastianelli G, Abagnale C, Genovese F, Messina R. Neuroimaging Studies of Migraine Without Aura. In: Petrušić, I., Wang, Y. (eds). Neuroimaging of Headache Disorders. Headache. [Internet]. Springer, Cham. 2025; p. 83–109. doi: https://doi.org/pwwz
Akerman S, Goadsby PJ. Topiramate inhibits cortical spreading depression in rat and cat: impact in migraine aura. Neuroreport. [Internet]. 2005; 16(12):1383-1387. doi: https://doi.org/bptc2g
Mohos V, Harmat M, Kun J, Aczél T, Zsidó BZ, Kitka T, Farkas S, Pintér E, Helyes Z. Topiramate inhibits adjuvant- induced chronic orofacial inflammatory allodynia in the rat. Front. Pharmacol. [Internet]. 2024; 15:1461355. doi: https://doi.org/pww2
Fan D, Leng W, Zhang L. Systematic evaluation and meta- analysis of Flunarizine Hydrochloride combined with traditional Chinese medicine decoction in the treatment of migraine headaches, Clinics. [Internet]. 2024; 79:100431, doi: https://doi.org/pww3
Saklani P, Khan H, Gupta S, Kaur A, Singh, TG. Neuropeptides: Potential neuroprotective agents in ischemic injury. Life Sci. [Internet]. 2022; 288:120186. doi: https://doi.org/pww4
Guo Y, Cheng Y, An J, Qi Y, Luo G. Neuropeptide changes in an improved migraine model with repeat stimulations. Transl. Neurosci. 2021; 12(1), 523-532. doi: https://doi.org/pww5
Gülsün M, Tamam L. Özçelik F. Neuropeptide Y and Stress. Psikiyatride güncel yaklaşımlar. [Internet]. 2012; 4(1):14-36. doi: https://doi.org/fnwhjs
Zhang Y, Liu CY, Chen WC, Shi YC, Wang CM, Lin S, He HF. Regulation of neuropeptide Y in body microenvironments and its potential application in therapies: a review. Cell & Biosci. [Internet]. 2021; 11:151. doi: https://doi.org/gnv9hq
