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Antiangiogenic effect of bevacizumab in monoclonal antibodies in experimental inflammatory pain model

Year 2019, Volume: 44 Issue: Supplement 1, 33 - 40, 29.12.2019
https://doi.org/10.17826/cumj.532813

Abstract

Purpose: This study aimed to investigate the possible anti-nociceptive, anti-inflammatory and anti-edema effects of systemic (intaperitoneal) and local (intraplantar) bevacizumab in the experimental inflammation model (introduced with Carrageenan). 

Materials and Methods: Sensory functions of rats with inflammatory pain (using Carrageenan (CAR)), performed using healthy and CAR, systemically or locally anti-hypernaphyseceptive effects of bevacizumab at different doses, using thermal plantar test (for hyperalgesia), dynamic plantaraesthesiometer (for allodynia) anti-edema effects were evaluated by measuring paw masses.

Results: The application of local intraplantar (IPL) or intraperitoneal (IP) bevacizumab in healthy rats used as controls in the studies did not cause any change in the thermal latency or mechanical threshold parameters in neurobiophysical tests. CAR application caused a decrease in mechanical threshold and thermal latency parameters and an increase in paw mass. 

Conclusion: Systemic applications of bevacizumab may show more anti-hyperalgesic and anti-allodinic effects. Hyperalgesia pain following CAR application was determined by thermal latency measurements using a stimulus. The resulting hyperalgesia was effectively suppressed by systemic bevacizumab for a long time. 


References

  • Loeser JD, Melzack R. Pain: an overview. Lancet, 1999;353:1607-1609.
  • Bars DL, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001;53:597–652.
  • Steeds CE. The anatomy and physiology of pain. Surgery (Oxford).2009; 507-511.
  • Andrew D, Greenspan JD. Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J. Neurophysiol.1999;82:2649–56.
  • Fechoa K, Nackley AG, Wu Y, Maixner W. Basal and carrageenan-induced pain behavior in Sprague– Dawley, Lewis and Fischer rats. Physiol Behav. 2005;85:177-86.
  • Türk Farmakoloji Derneği XXII. Eğitim Toplantısı Doğu Akdeniz Farmakoloji Topluluğu (DAFT) İşbirliğiyle İnflamasyon ve Ağrı 29 Mayıs 2015 Çukurova Üniversitesi Akif Kansu Toplantı Salonu, Balcalı, Adana.
  • Aydın ON. Ağrı ve ağrı mekanizmalarına güncel bakış. 2002.
  • Kayhan Z. Klinik Anestezi. 2. Baskı İstanbul: Logos Yayıncılık, 1997: 759-87.
  • Kidd BL, Urban LA. Mechanisms of inflammatory pain. British journal of anaesthesia. 2001;3-11.
  • Güneş Y, et al. Ağrının İletilmesinde N-Metil D-Aspartat Reseptörlerinin Rolü. Cukurova Medical Journal. 2012;37.1.
  • Martin TJ, Eisenach JC. Pharmacology of opioid and nonopioid analgesics in chronic pain states. J. Pharmacol. Exp. Ther. 2001; 299:811-817.
  • Sawynok J, Topical and Peripherally Acting Analgesics. Pharmacol. Rev. 2003; 55:1-20.
  • Hargreaves K, Dubner R, Broun F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1998;32:77-8.
  • Millan MJ. The induction of pain: an integrative review. Progress in neurobiology. 1999;1-164.
  • Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932-6.
  • Çukadar N, Baran F, Özsoy KE, Uyanık FB, Sürer T, Mert T, Güneş Y. Nociceptive Effects of Locally Treated Metoprolol. Cukurova Med J. 2015;40:258-266.
  • Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Hematol 2001;106:148-156.
  • Nazmiye E. Vasküler Endotelyal Büyüme Faktörü ve Anti-VEGF Ajanlar.
  • Shih T, Lindley C. Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther. 2006;28:1779–1802.
  • Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem. 1991;47:211-8.
  • Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991;266:11947-54.
  • Ferrara N, Houck KA, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992;13:18-32.
  • Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27-31.
  • John EH. Guyton and Hall medical physiology. Elsevier 2010.
  • Mert T, Ocal I, Gunay I. Pain relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation. Int Rad Biol. 2014;95-103.
  • Mert T, Oksuz H, Tugtag B, Kilinc M, Senoglu N, Bilgin R. Modulating actions of NMDA receptors on pronociceptive effects of locally injected remifentanil in diabetic rats. Pharmacol Rep. 2014;66:1065–10722.
  • Mert T, Gunes Y, Gunay I. Local analgesic efficacy of tramadol following intraplantar injection. Eur. J. Pharmacol Eur. 2007:558, 68-72.
  • Cébe SS, Zehnder-FA, Ballmer HK. The role of VEGF receptors in angiogenesis; complex partnerships. Cell Mol Life Sci. 2006;63:601-615.
  • Noonan SA, Morrissey ME, Martin P, Biniecka M, Ó'Meachair S, Maguire A, O'Donoghue D. Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment. Oncotarget. 2018;9:12,105-36.
  • Ribatti D. The inefficacy of antiangiogenic therapies. Journal of angiogenesis research. 2010;2.1:27.
  • Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860-867.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
  • Kong SY, Bostick RM, Flanders WD, McClellan WM, Thyagarajan B, Gross MD, Judd S, Goodman M. Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation. Cancer Epidemiol Biomarkers Prev. 2014;23:545-554.
  • Arimura S, et al. The effect of triamcinolone acetonide or bevacizumab on the levels of pro-inflammatory cytokines after retinal laser photocoagulation in pigmented rabbits. Experimental eye research. 2016;149:1-7.
  • Qu CY, Zheng Y, Zhou M, et al. Value of bevacizumab in treatment of colorectal cancer: A meta-analysis. World J Gastroenterol. 2015;21(16):5072-80.
  • Klein A, Loewenstein A. Therapeutic Monoclonal Antibodies and Fragments: Bevacizumab. Dev Ophthalmol. 2016;55:232-4.
  • Amoaku WMK, Saker S, Stewart E A. A review of therapies for diabetic macular oedema and rationale for combination therapy. Eye. 2015; 29:9,1115.

Monoklonal antikorlardan bevacizumab'ın deneysel inflamatuar ağrı modelinde antianjiyogenik etkisi

Year 2019, Volume: 44 Issue: Supplement 1, 33 - 40, 29.12.2019
https://doi.org/10.17826/cumj.532813

Abstract

Amaç: Bu çalışmada, deneysel inflamatuar modelinde (Carrageenan kullanılarak meydana getirilen) sistemik (intraperitoneal: IP) ve lokal (intraplantar: IPL) olarak uygulanan bevacizumab’ın muhtemel anti-nosiseptif, anti-inflamatuar ve anti-ödem etkilerinin araştırılması amaçlanmıştır.

Gereç ve Yöntem: Sağlıklı ve Carrageenan (CAR) kullanılarak gerçekleştirilen inflamatuar ağrılı sıçanların duysal fonksiyonları termal plantar test (hiperaljezi için), dinamik plantar estesiometre (allodini için) kullanılarak, farklı dozlarda bevacizumab’ın sistemik veya lokal anti-hipernosiseptif etkileri, pençe kütleleri ölçülerek de anti-ödem etkileri değerlendirildi. Biyokimyasal analizler için sıçan pençelerinden alınan örnekler kullanıldı.

Bulgular: Kontrol olarak kullanılan sağlıklı sıçanlarda lokal (intraplantar: IPL) veya sistemik (intraperitoneal: IP) bevacizumab uygulamasının nörobiyofizik testlerde termal latans veya mekanik eşik parametrelerinde herhangi bir değişime neden olmadığı görüldü. CAR uygulaması mekanik eşik ve termal latans parametresinde düşüşlere ve pençe kütlesinde artışa neden oldu. 

Sonuç: Çalışmalarımızda, bevacizumab’ın özellikle sistemik uygulamalarının daha fazla anti-hiperaljezik ve anti-allodinik etkiler gösterebileceği belirlendi. CAR uygulaması sonrası ortaya çıkan hiperaljezi, ağrılı bir uyaranın kullanıldığı termal latans ölçümleriyle belirlendi. Ortaya çıkan hiperaljezi, sistemik bevacizumab tarafından etkili bir şekilde uzun süreli baskılandı. 


References

  • Loeser JD, Melzack R. Pain: an overview. Lancet, 1999;353:1607-1609.
  • Bars DL, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001;53:597–652.
  • Steeds CE. The anatomy and physiology of pain. Surgery (Oxford).2009; 507-511.
  • Andrew D, Greenspan JD. Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J. Neurophysiol.1999;82:2649–56.
  • Fechoa K, Nackley AG, Wu Y, Maixner W. Basal and carrageenan-induced pain behavior in Sprague– Dawley, Lewis and Fischer rats. Physiol Behav. 2005;85:177-86.
  • Türk Farmakoloji Derneği XXII. Eğitim Toplantısı Doğu Akdeniz Farmakoloji Topluluğu (DAFT) İşbirliğiyle İnflamasyon ve Ağrı 29 Mayıs 2015 Çukurova Üniversitesi Akif Kansu Toplantı Salonu, Balcalı, Adana.
  • Aydın ON. Ağrı ve ağrı mekanizmalarına güncel bakış. 2002.
  • Kayhan Z. Klinik Anestezi. 2. Baskı İstanbul: Logos Yayıncılık, 1997: 759-87.
  • Kidd BL, Urban LA. Mechanisms of inflammatory pain. British journal of anaesthesia. 2001;3-11.
  • Güneş Y, et al. Ağrının İletilmesinde N-Metil D-Aspartat Reseptörlerinin Rolü. Cukurova Medical Journal. 2012;37.1.
  • Martin TJ, Eisenach JC. Pharmacology of opioid and nonopioid analgesics in chronic pain states. J. Pharmacol. Exp. Ther. 2001; 299:811-817.
  • Sawynok J, Topical and Peripherally Acting Analgesics. Pharmacol. Rev. 2003; 55:1-20.
  • Hargreaves K, Dubner R, Broun F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1998;32:77-8.
  • Millan MJ. The induction of pain: an integrative review. Progress in neurobiology. 1999;1-164.
  • Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932-6.
  • Çukadar N, Baran F, Özsoy KE, Uyanık FB, Sürer T, Mert T, Güneş Y. Nociceptive Effects of Locally Treated Metoprolol. Cukurova Med J. 2015;40:258-266.
  • Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Hematol 2001;106:148-156.
  • Nazmiye E. Vasküler Endotelyal Büyüme Faktörü ve Anti-VEGF Ajanlar.
  • Shih T, Lindley C. Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther. 2006;28:1779–1802.
  • Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem. 1991;47:211-8.
  • Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991;266:11947-54.
  • Ferrara N, Houck KA, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992;13:18-32.
  • Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27-31.
  • John EH. Guyton and Hall medical physiology. Elsevier 2010.
  • Mert T, Ocal I, Gunay I. Pain relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation. Int Rad Biol. 2014;95-103.
  • Mert T, Oksuz H, Tugtag B, Kilinc M, Senoglu N, Bilgin R. Modulating actions of NMDA receptors on pronociceptive effects of locally injected remifentanil in diabetic rats. Pharmacol Rep. 2014;66:1065–10722.
  • Mert T, Gunes Y, Gunay I. Local analgesic efficacy of tramadol following intraplantar injection. Eur. J. Pharmacol Eur. 2007:558, 68-72.
  • Cébe SS, Zehnder-FA, Ballmer HK. The role of VEGF receptors in angiogenesis; complex partnerships. Cell Mol Life Sci. 2006;63:601-615.
  • Noonan SA, Morrissey ME, Martin P, Biniecka M, Ó'Meachair S, Maguire A, O'Donoghue D. Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment. Oncotarget. 2018;9:12,105-36.
  • Ribatti D. The inefficacy of antiangiogenic therapies. Journal of angiogenesis research. 2010;2.1:27.
  • Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860-867.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
  • Kong SY, Bostick RM, Flanders WD, McClellan WM, Thyagarajan B, Gross MD, Judd S, Goodman M. Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation. Cancer Epidemiol Biomarkers Prev. 2014;23:545-554.
  • Arimura S, et al. The effect of triamcinolone acetonide or bevacizumab on the levels of pro-inflammatory cytokines after retinal laser photocoagulation in pigmented rabbits. Experimental eye research. 2016;149:1-7.
  • Qu CY, Zheng Y, Zhou M, et al. Value of bevacizumab in treatment of colorectal cancer: A meta-analysis. World J Gastroenterol. 2015;21(16):5072-80.
  • Klein A, Loewenstein A. Therapeutic Monoclonal Antibodies and Fragments: Bevacizumab. Dev Ophthalmol. 2016;55:232-4.
  • Amoaku WMK, Saker S, Stewart E A. A review of therapies for diabetic macular oedema and rationale for combination therapy. Eye. 2015; 29:9,1115.
There are 37 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research
Authors

Selma Yaman 0000-0002-9301-9119

Nursima Çukadar This is me 0000-0001-5068-1770

Furkan Baran This is me 0000-0003-3963-103X

Fatih Burak Uyanık This is me 0000-0001-9737-3134

Metin Kılınç 0000-0002-1623-0201

Tufan Mert 0000-0002-5926-9210

Publication Date December 29, 2019
Acceptance Date June 17, 2019
Published in Issue Year 2019 Volume: 44 Issue: Supplement 1

Cite

MLA Yaman, Selma et al. “Monoklonal Antikorlardan bevacizumab’ın Deneysel Inflamatuar ağrı Modelinde Antianjiyogenik Etkisi”. Cukurova Medical Journal, vol. 44, 2019, pp. 33-40, doi:10.17826/cumj.532813.