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Akciğer Mast Hücre Davranışının Migren Sıçan Modelinde İncelenişi: Migren Baş Ağrısı İçin Çıkarımlar

Yıl 2018, Cilt: 23 Sayı: 3, 151 - 156, 26.09.2018
https://doi.org/10.21673/anadoluklin.429905

Öz

Amaç: Bu çalışmada sıçanlarda nitrogliserin ile oluşturulan migren modeli kullanılarak akciğer mast hücrelerinin
migrendeki muhtemel rolünü araştırmak amaçlanmıştır.

Gereç ve Yöntemler: Otuz beş yetişkin erkek Wistar sıçan beş gruba bölündü. Tüm uygulamalar intraperitoneal
yoldan olmak üzere; NS grubuna 0,2 ml normal salin (serum fizyolojik), NTG grubuna 10 mg/kg
nitrogliserin, vehikül NTG grubuna 0,2 ml normal salin içinde %0,1’lik etanol, L-NAME+NTG grubuna 50
mg/kg L-NAME + nitrogliserin, NS+NTG grubuna ise 0,2 ml normal salin + nitrogliserin uygulandı. Nitrogliserin
ve diğer uygulamalardan iki saat sonra sıçanlar anestezi altında 150 ml %4’lük paraformaldehit ile
intrakardiyak olarak perfüze edildi. Akciğerler alındı ve mast hücrelerini gözlemlemek için toluidin mavisi
ile boyandı. Veriler tek yönlü varyans analizi ile incelendi.

Bulgular: Nitrogliserin akciğer mast hücrelerinin hem sayısında (94±3,8’den 131±6,7’ye; p=0,0035) hem
de degranülasyon yüzdesinde (%11,8±1,3’ten %35,5±5,7’ye; p=0,003) anlamlı bir artış sağladı. L-NAME
ise akciğer mast hücrelerinin sayı ve degranülasyonu üzerinde nitrogliserinin yol açtığı bu etkileri önledi,
böylece akciğer mast hücrelerinin nitrogliserin ile tetiklenerek artan sayısını ve degranülasyon yüzdesini
ayrı ayrı azalttı.

Tartışma ve Sonuç: Bulgularımız nitrogliserin ile oluşturulan migren sıçan modelinde nitrogliserin uygulamasının
akciğer mast hücrelerinin sayısında ve degranülasyonunda bir artışa yol açtığını göstermiştir.
Ayrıca L-NAME’nin bu etkileri önlemiş olması, nitrogliserin kaynaklı nitrik oksidin direkt veya indirekt olarak
akciğer mast hücrelerinin aktivasyonuna yol açtığını düşündürmektedir. Bu çalışmada elde edilen
sonuçlar akciğer mast hücrelerinin migrendeki rolü üzerine yapılacak yeni araştırmalara öncülük edebilir. 

Kaynakça

  • 1. Héron A, Dubayle D. A focus on mast cells and pain. J Neuroimmunol 2013; 264(1-2):1-7.2. Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, et al. Mast cells and inflammation. Biochim Biophys Acta. 2012; 1822(1): 21-33. 3. Kilinc E, Dagistan Y, Cetinkaya A, Tore F. The comparison of effects of applications of compound 48/80 and mast cell mediator suspension on inflammation in rats: A methodological study for acute inflammatory pain. Clin Exp Health Sci 2018. DOI: 10.5152/clinexphealthsci.2018.923.4. Kilinc E, Dagistan Y, Kotan B, Cetinkaya A. Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats. Physiol Int. 2017; 104(1): 15-24. 5. Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM. Mast cell degranulation activates a pain pathway underlying migraine headache. Pain. 2007; 130(1-2): 166-76. 6. Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A. The role of mast cells in migraine pathophysiology. Brain Res Brain Res Rev. 2005; 49(1): 65-76. 7. Kilinc E, Dagistan Y, Kukner A, Yilmaz B, Agus S, Soyler G, Tore F. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats. Clin Exp Pharmacol Physiol. 2018; 45(6): 536-46.8. Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018. doi: 10.1007/s00281-018-0676-y. 9. Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther. 2007; 322(2): 806-12. 10. Kilinc E, Guerrero-Toro C, Zakharov A, Vitale C, Gubert-Olive M, Koroleva K, et al. Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain. Neuropharmacology. 2017; 116: 160-73. 11. Kemper RH, Meijler WJ, Korf J, Ter Horst GJ. Migraine and function of the immune system: a meta-analysis of clinical literature published between 1966 and 1999. Cephalalgia. 2001; 21(5): 549-57.12. Heatley RV, Denburg JA, Bayer N, Bienenstock J. Increased plasma histamine levels in migraine patients. Clin Allergy. 1982; 12(2): 145-9.13. Haimart M, Pradalier A, Launay JM, Dreux C, Dry J. Whole blood and plasma histamine in common migraine. Cephalalgia. 1987; 7(1): 39-42.14. Gazerani P, Pourpak Z, Ahmadiani A, Hemmati A, Kazemnejad A. A correlation between migraine, histamine and immunoglobulin e. Scand J Immunol. 2003; 57(3): 286-90.15. Ramachandran R, Bhatt DK, Ploug KB, Hay-Schmidt A, Jansen-Olesen I, Gupta S, et al. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation. Cephalalgia. 2014; 34(2): 136-47.16. Pedersen SH, Ramachandran R, Amrutkar DV, Petersen S, Olesen J, Jansen-Olesen I. Mechanisms of glyceryl trinitrate provoked mast cell degranulation. Cephalalgia. 2015; 35(14): 1287-97.17. Jansen-Olesen I, Hougaard Pedersen S. PACAP and its receptors in cranial arteries and mast cells. J Headache Pain. 2018; 19(1):16. 18. Malhotra R. Understanding migraine: Potential role of neurogenic inflammation. Annals of Indian Academy of Neurology. 2016; 19(2): 175-82.19. Davey G, Sedgwick P, Maier W, Visick G, Strachan DP, Anderson HR. Association between migraine and asthma: matched case-control study. Br J Gen Pract. 2002; 52(482): 723-7.20. Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA. Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007; 47(2): 204-12.21. Kaleagasi H, Özgür E, Özge C, Özge A. Bronchial hyper-reactivity in migraine without aura: is it a new clue for inflammation? Headache. 2011; 51(3):426-31.22. Ozge A, Ozge C, Oztürk C, Kaleagasi H, Ozcan M, Yalçinkaya DE, et al. The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening. Cephalalgia. 2006; 26(2): 172-9.23. Peng YH, Chen KF, Kao CH, Chen HJ, Hsia TC, Chen CH, et al. Risk of Migraine in Patients With Asthma: A Nationwide Cohort Study. Medicine (Baltimore). 2016; 95(9): e2911.24. Turan MO, Susuz ÇÇ, Turan PA. Presence of Headache and Migraine in Asthma Patients. Turk Thorac J. 2017; 18: 47-51.25. Dirican N, Demirci S, Cakir M. The relationship between migraine headache and asthma features. Acta Neurol Belg. 2017; 117(2): 531-36. 26. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008; 88(3): 1183-241.27. Tfelt-Hansen P, Daugaard D, Lassen LH, Iversen HK, Olesen J. Prednisolone reduces nitric oxide-induced migraine. Eur J Neurol. 2009; 16(10): 1106-11.28. Coleman JW. Nitric oxide: a regulator of mast cell activation and mast cell-mediated inflammation. Clinical and Experimental Immunology. 2002; 129(1): 4-10. 29. Sekar Y, Moon TC, Muñoz S, Befus AD. Role of nitric oxide in mast cells: controversies, current knowledge, and future applications. Immunol Res. 2005; 33(3): 223-39. 30. Eastmond NC, Banks EM, Coleman JW. Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis. J Immunol. 1997; 159(3): 1444-50.

An Investigation of Lung Mast Cell Behavior in a Rat Model of Migraine: Implications for Migraine Headache

Yıl 2018, Cilt: 23 Sayı: 3, 151 - 156, 26.09.2018
https://doi.org/10.21673/anadoluklin.429905

Öz

Aim: In this study, we aimed to investigate the potential role of lung mast cells in migraine by using a
nitroglycerin-induced migraine model in rats.

Materials and Methods: Thirty-five adult male Wistar rats were divided into five groups. Each treatment
being performed intraperitoneally, the NS group received 0.2 ml normal saline, the NTG group 10 mg/kg
nitroglycerin, the NTG vehicle group 0.2 ml 0.1% ethanol in normal saline, the L-NAME+NTG group 50
mg/kg L-NAME + nitroglycerin, and the NS+NTG group normal saline + nitroglycerin. Two hours after the
nitroglycerin and other treatments, the rats under anesthesia were intracardially perfused with a solution
of 150 ml 4% paraformaldehyde. The lungs were harvested and stained with toluidine blue to observe
mast cells. The data were analyzed by using one-way ANOVA.

Results: Nitroglycerin increased significantly both number (from 94±3.8 to 131±6.7, p=0.0035) and percent
of degranulation (from 11.8±1.3% to 35.5±5.7%, p=0.003) of lung mast cells. However, L-NAME
prevented the effects of nitroglycerin on the number and degranulation of lung mast cells, attenuating
the increase in both number (from 136±5.1 to 93±2.5, p=0.0011) and degranulation percentage of lung
mast cells (from 37.3±1.0% to 13.6±3.1%, p=0.001) induced by nitroglycerin.

Discussion and Conclusion: Our findings demonstrate that nitroglycerin treatment leads to an increase
in the number and degranulation of lung mast cells in a rat model of migraine induced by nitroglycerin.
Moreover, L-NAME prevented these effects, suggesting that nitric oxide released from nitroglycerin directly
or indirectly leads to the activation of lung mast cells. The results obtained in the current study can
pioneer new research on the role of lung mast cells in migraine. 

Kaynakça

  • 1. Héron A, Dubayle D. A focus on mast cells and pain. J Neuroimmunol 2013; 264(1-2):1-7.2. Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, et al. Mast cells and inflammation. Biochim Biophys Acta. 2012; 1822(1): 21-33. 3. Kilinc E, Dagistan Y, Cetinkaya A, Tore F. The comparison of effects of applications of compound 48/80 and mast cell mediator suspension on inflammation in rats: A methodological study for acute inflammatory pain. Clin Exp Health Sci 2018. DOI: 10.5152/clinexphealthsci.2018.923.4. Kilinc E, Dagistan Y, Kotan B, Cetinkaya A. Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats. Physiol Int. 2017; 104(1): 15-24. 5. Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM. Mast cell degranulation activates a pain pathway underlying migraine headache. Pain. 2007; 130(1-2): 166-76. 6. Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A. The role of mast cells in migraine pathophysiology. Brain Res Brain Res Rev. 2005; 49(1): 65-76. 7. Kilinc E, Dagistan Y, Kukner A, Yilmaz B, Agus S, Soyler G, Tore F. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats. Clin Exp Pharmacol Physiol. 2018; 45(6): 536-46.8. Ramachandran R. Neurogenic inflammation and its role in migraine. Semin Immunopathol. 2018. doi: 10.1007/s00281-018-0676-y. 9. Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther. 2007; 322(2): 806-12. 10. Kilinc E, Guerrero-Toro C, Zakharov A, Vitale C, Gubert-Olive M, Koroleva K, et al. Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain. Neuropharmacology. 2017; 116: 160-73. 11. Kemper RH, Meijler WJ, Korf J, Ter Horst GJ. Migraine and function of the immune system: a meta-analysis of clinical literature published between 1966 and 1999. Cephalalgia. 2001; 21(5): 549-57.12. Heatley RV, Denburg JA, Bayer N, Bienenstock J. Increased plasma histamine levels in migraine patients. Clin Allergy. 1982; 12(2): 145-9.13. Haimart M, Pradalier A, Launay JM, Dreux C, Dry J. Whole blood and plasma histamine in common migraine. Cephalalgia. 1987; 7(1): 39-42.14. Gazerani P, Pourpak Z, Ahmadiani A, Hemmati A, Kazemnejad A. A correlation between migraine, histamine and immunoglobulin e. Scand J Immunol. 2003; 57(3): 286-90.15. Ramachandran R, Bhatt DK, Ploug KB, Hay-Schmidt A, Jansen-Olesen I, Gupta S, et al. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation. Cephalalgia. 2014; 34(2): 136-47.16. Pedersen SH, Ramachandran R, Amrutkar DV, Petersen S, Olesen J, Jansen-Olesen I. Mechanisms of glyceryl trinitrate provoked mast cell degranulation. Cephalalgia. 2015; 35(14): 1287-97.17. Jansen-Olesen I, Hougaard Pedersen S. PACAP and its receptors in cranial arteries and mast cells. J Headache Pain. 2018; 19(1):16. 18. Malhotra R. Understanding migraine: Potential role of neurogenic inflammation. Annals of Indian Academy of Neurology. 2016; 19(2): 175-82.19. Davey G, Sedgwick P, Maier W, Visick G, Strachan DP, Anderson HR. Association between migraine and asthma: matched case-control study. Br J Gen Pract. 2002; 52(482): 723-7.20. Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA. Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007; 47(2): 204-12.21. Kaleagasi H, Özgür E, Özge C, Özge A. Bronchial hyper-reactivity in migraine without aura: is it a new clue for inflammation? Headache. 2011; 51(3):426-31.22. Ozge A, Ozge C, Oztürk C, Kaleagasi H, Ozcan M, Yalçinkaya DE, et al. The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening. Cephalalgia. 2006; 26(2): 172-9.23. Peng YH, Chen KF, Kao CH, Chen HJ, Hsia TC, Chen CH, et al. Risk of Migraine in Patients With Asthma: A Nationwide Cohort Study. Medicine (Baltimore). 2016; 95(9): e2911.24. Turan MO, Susuz ÇÇ, Turan PA. Presence of Headache and Migraine in Asthma Patients. Turk Thorac J. 2017; 18: 47-51.25. Dirican N, Demirci S, Cakir M. The relationship between migraine headache and asthma features. Acta Neurol Belg. 2017; 117(2): 531-36. 26. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008; 88(3): 1183-241.27. Tfelt-Hansen P, Daugaard D, Lassen LH, Iversen HK, Olesen J. Prednisolone reduces nitric oxide-induced migraine. Eur J Neurol. 2009; 16(10): 1106-11.28. Coleman JW. Nitric oxide: a regulator of mast cell activation and mast cell-mediated inflammation. Clinical and Experimental Immunology. 2002; 129(1): 4-10. 29. Sekar Y, Moon TC, Muñoz S, Befus AD. Role of nitric oxide in mast cells: controversies, current knowledge, and future applications. Immunol Res. 2005; 33(3): 223-39. 30. Eastmond NC, Banks EM, Coleman JW. Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis. J Immunol. 1997; 159(3): 1444-50.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ORJİNAL MAKALE
Yazarlar

Erkan Kılınç

Cemre Nur Balcı

Yayımlanma Tarihi 26 Eylül 2018
Kabul Tarihi 6 Temmuz 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 23 Sayı: 3

Kaynak Göster

Vancouver Kılınç E, Balcı CN. An Investigation of Lung Mast Cell Behavior in a Rat Model of Migraine: Implications for Migraine Headache. Anadolu Klin. 2018;23(3):151-6.

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