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The relationship between neuropathic pain and serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, VEGF-A levels in fibromyalgia patients and molecular docking results

Yıl 2023, Cilt: 48 Sayı: 2, 522 - 534, 02.07.2023

Özlem Balbaloğlu Nihal İnandıklıoglu Kayode Yomi Raheem

https://doi.org/10.17826/cumj.1273163

Öz

Purpose: The most important clinical finding of fibromyalgia syndrome (FMS) is pain. Its etiology has not been fully elucidated. This study was planned to determine the relationship between endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-a, VEGF-A levels and pain/neuropathic pain in FMS patients.
Materials and Methods: Forty-four FMS patients who met the inclusion criteria and 44 age-matched premenopausal healthy controls were recruited. The fibromyalgia group was evaluated in terms of Visual Analog Scale, Beck Depression Scale, Beck Anxiety Scale, Fibromyalgia Impact Questionnaire and LANSS Pain Scale. Serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A values were determined by the ELISA method. Protein-protein interaction was evaluated by molecular docking analysis. Bioinformatics analysis was performed using the STRING v 11.5 protein interaction tool.
Results: Endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A were significantly higher in FMS patients than the control group. 24 of 44 patients had neuropathic pain. No correlation was found between pain/neuropathic pain and serum markers levels. High interaction and homology scores of the proteins were defined.
Conclusion: The pain/neuropathic pain relationship of these markers could not be determined, but the calculated binding energies and activities of the proteins provided important clues for future studies.

Anahtar Kelimeler

Cytokine Fibromyalgia Molecular Docking Neuropathic Pain

Destekleyen Kurum

Yozgat Bozok Üniversitesi

Proje Numarası

6602b-TF/19-301

Teşekkür

This study was funded by Yozgat Bozok University Scientific Research Project Unit (6602b-TF/19-301), and was conducted at Yozgat Bozok University Hospital.

Kaynakça

  • Bazzichi L, Giacomelli C, Consensi A, Giorgi V, Batticciotto A, Di Franco M et al. One year in review 2020: fibromyalgia. Clin Exp Rheumatol. 2020;38:3-8.
  • Küçükşen S, Genç E, Yılmaz H, Sallı A, Gezer İA, Karahan AY et al. The prevalence of fibromyalgia and its relation with headache characteristics in episodic migraine. Clin Rheumatol. 2013;32:983-90.
  • Alles SRA, Smith PA. Etiology and pharmacology of neuropathic pain. Pharmacol Rev. 2018;70:315-47.
  • Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice ASC et al. A new definition of neuropathic pain. Pain. 2011;152:2204-05.
  • Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000;47:123-28.
  • Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, et al. Cytokine-induced sickness behavior. Brain Behav Immun. 2003;17:112-118.
  • Watkins LR, Maier SF. The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol. 2000;51:29-57.
  • Feng J, Zhang Z, Wu X, Mao A, Chang F, Deng X et al. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing. PLoS One. 2013;8:e65033.
  • Blanco I, Janciauskiene S, Nita I, Fernández-Bustillo E, Cárcaba V, Gallo C et al. Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia. Clin Rheumatol. 2010;29:189-97.
  • Mertoglu C, Gunay M, Yerligok O. Could endocan, a marker of inflammation and endothelial dysfunction, be a new diagnostic marker for fibromyalgia?. Clin Lab. 2018;64:405-10.
  • Nah SS, Lee H, Hong Y, Im J, Won H, Chang SH et al. Association between endothelin‑1 and fibromyalgia syndrome. Mol Med Rep. 2017;16:6234-39.
  • Sommer C. Zytokine bei neuropathischen Schmerzen [cytokines in neuropathic pain]. Anaesthesist. 2001;50:416-26.
  • Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319-29.
  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-71.
  • Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893-7.
  • Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 2001;92:147-57.
  • Schrödinger LLC. The PyMOL molecular graphics system. Version 2.5.2. 2010.
  • Rakhmetov A, Lee SP, Grebinyk D, Ostapchenko L, Chae HZ. Simulation of peroxiredoxin II and brain-type creatine Kinase protein-protein interaction using the on-line docking server ClusPro 2.0. J App Pharm Sci. 2015;5:011-016.
  • Kozakov D, Beglov D, Bohnuud T, Mottarella SE, Xia B, Hall DR et al. How good is automated protein docking? Proteins. 2013;81:2159-66.
  • Chuang GY, Kozakov D, Brenke R, Comeau SR, Vajda S. DARS (Decoys As the Reference State) potentials for protein-protein docking. Biophys J. 2008;95:4217-27.
  • Xue LC, Rodrigues JP, Kastritis PL, Bonvin AM, Vangone A. PRODIGY: a web server for predicting the binding affinity of protein-protein complexes. Bioinformatics. 2016;32:3676-78.
  • Vangone A, Bonvin AM. Contacts-based prediction of binding affinity in protein-protein complexes. Elife. 2015;4:e07454.
  • Valdés H, Díaz N, Suárez D, Fernández-Recio J. Interdomain Conformations in the full-length MMP-2 enzyme explored by protein-protein docking calculations using pyDock. J Chem Theory Comput. 2010;6:2204-13.
  • Kastritis PL, Bonvin AM. Are scoring functions in protein-protein docking ready to predict interactomes? Clues from a novel binding affinity benchmark [published correction appears in J Proteome Res 2011 Feb 4;10:921-2]. J Proteome Res. 2010;9:2216-25.
  • Mottin M, Souza PC, Skaf MS. Molecular recognition of PPARγ by kinase Cdk5/p25: insights from a combination of protein-protein docking and adaptive biasing force simulations. J Phys Chem B. 2015;119:8330-39.
  • Qiao B, Lopez L, Olvera de la Cruz M. "Mirror"-like protein dimers stabilized by local heterogeneity at protein surfaces. J Phys Chem B. 2019;123:3907-15.
  • Soulier JL, Russo O, Giner M, Rivail L, Berthouze M, Ongeri S et al. Design and synthesis of specific probes for human 5-HT4 receptor dimerization studies. J Med Chem. 2005;48:6220-28.
  • Koldsø H, Andersen OJ, Nikolajsen CL, Scavenius C, Sørensen CS, Underhaug J et al. Early events in the amyloid formation of the A546T mutant of transforming growth factor β-induced protein in corneal dystrophies compared to the nonfibrillating R555W and R555Q mutants. Biochemistry. 2015;54:5546-5556.
  • Kahler U, Kamenik AS, Waibl F, Kraml J, Liedl KR. Protein-protein binding as a two-step mechanism: preselection of encounter poses during the binding of BPTI and trypsin. Biophys J. 2020;119:652-66.
  • Cui W, Wei Z, Chen Q, Cheng Y, Geng L, Zhang J et al. Structure-based design of peptides against G3BP with cytotoxicity on tumor cells. J Chem Inf Model. 2010;50:380-87.
  • Yang Z, Bogdan P, Nazarian S. An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study. Sci Rep. 2021;11:3238.
  • Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Semin Immunopathol. 2018;40:291-300.
  • Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, et al. Age-related impairment of vascular structure and functions. Aging Dis. 2017;8:590-610.
  • Wang H, Moser M, Schiltenwolf M, Buchner M. Circulating cytokine levels compared to pain in patients with fibromyalgia - a prospective longitudinal study over 6 months. J Rheumatol. 2008;35:1366-70.
  • Ang DC, Moore MN, Hilligoss J, Tabbey R. MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study. Pain Med. 2011;12:1154-61.
  • Yoshio T, Masuyama J, Mimori A, Takeda A, Minota S, Kano S. Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. Ann Rheum Dis. 1995;54:361-65.
  • Pache M, Schwarz HA, Kaiser HJ, Wüest P, Klöti M, Dubler B, et al. Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis. Med Sci Monit. 2002;8:CR616-CR619.
  • Pache M, Ochs J, Genth E, Mierau R, Kube T, Flammer J. Increased plasma endothelin-1 levels in fibromyalgia syndrome. Rheumatology (Oxford). 2003;42:493-94.
  • Bauer V, Sotníková R. Nitric oxide--the endothelium-derived relaxing factor and its role in endothelial functions. Gen Physiol Biophys. 2010;29:319-40.
  • Cunningham ME, Huribal M, Bala RJ, McMillen MA. Endothelin-1 and endothelin-4 stimulate monocyte production of cytokines. Crit Care Med. 1997;25:958-64.
  • Hans G, Deseure K, Adriaensen H. Endothelin-1-induced pain and hyperalgesia: a review of pathophysiology, clinical manifestations and future therapeutic options. Neuropeptides. 2008;42:119-32.
  • Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549-80.
  • Delehedde M, Devenyns L, Maurage CA, Vivès RR. Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan. Int J Cell Biol. 2013;2013:705027.
  • Mahmoud EA, Moneim WA, Shaker OG, Ghalwash DM. Expression of endocan and vascular endothelial growth factor in recurrent minor aphthous ulcers. J Clin Exp Dent. 2019;11:e534-e541.
  • Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev. 2009;89:607-48.
  • Lin J, Li G, Den X, Xu C, Liu S, Gao Y et al. VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X₂(/)₃ receptor of primary sensory neurons. Brain Res Bull. 2010;83:284-91.
  • Lee HL, Oh J, Yun Y, Lee HY, You Y, Che L, et al. Vascular endothelial growth factor-expressing neural stem cell for the treatment of neuropathic pain. Neuroreport. 2015;26:399-404.
  • Lee GW, Son JY, Lee AR, Ju JS, Bae YC, Ahn DK. Central VEGF-A pathway plays a key role in the development of trigeminal neuropathic pain in rats. Mol Pain. 2019;15:1744806919872602.
  • Kim SK, Kim KS, Lee YS, Park SH, Choe JY. Arterial stiffness and proinflammatory cytokines in fibromyalgia syndrome. Clin Exp Rheumatol. 2010;28:S71-S77.
  • Tas A, Hayta E, Karadag A, Zontul C, Ozmen E, Aydin S, et al. Potassium ion channel protein (KCNH) levels in patients with fibromyalgia syndrome. Cell Mol Biol. 2022;67:451-57

Fibromiyalji hastalarında nöropatik ağrı ile serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, VEGF-A düzeyleri arasındaki ilişki ve moleküler docking sonuçları

Yıl 2023, Cilt: 48 Sayı: 2, 522 - 534, 02.07.2023

Özlem Balbaloğlu Nihal İnandıklıoglu Kayode Yomi Raheem

https://doi.org/10.17826/cumj.1273163

Öz

Amaç: Fibromiyalji sendromunun (FMS) en önemli klinik bulgusu ağrıdır. Etiyolojisi tam olarak aydınlatılamamıştır. Bu çalışma FMS hastalarında endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-a ve VEGF-A düzeylerinin ağrı/nöropatik ağrı ile ilişkisini belirlemek amacıyla planlandı.
Gereç ve Yöntem: Çalışmaya dâhil edilme kriterlerini karşılayan 44 FMS hastası ve yaşları eşleştirilmiş 44 premenopozal sağlıklı kontrol alındı. Fibromiyalji grubu Visual Analog Ölçeği, Beck Depresyon Ölçeği, Beck Anksiyete Ölçeği, Fibromiyalji Etki Anketi ve LANSS Ağrı Ölçeği açısından değerlendirildi. Serum endokan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α ve VEGF-A değerleri ELISA yöntemi ile belirlendi. Protein-protein etkileşimi, moleküler docking analizi ile değerlendirildi. Biyoinformatik analiz, STRING v 11.5 protein aracı kullanılarak yapıldı.
Bulgular: Endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α ve VEGF-A FMS hastalarında kontrol grubuna göre anlamlı olarak yüksekti. 44 hastanın 24'ünde nöropatik ağrı vardı. Ağrı/nöropatik ağrı ile serum belirteçleri arasında korelasyon saptanamadı. Proteinlerin yüksek etkileşim ve homoloji skorları tanımlandı.
Sonuç: Bu belirteçlerin ağrı/nöropatik ağrı ilişkisi belirlenememiştir ancak proteinlerin hesaplanan bağlanma enerjileri ve aktiviteleri ilerideki çalışmalar için önemli ipuçları sağlamıştır.

Anahtar Kelimeler

Sitokin fibromiyalji moleküler yerleştirme nöropatik ağrı

Proje Numarası

6602b-TF/19-301

Kaynakça

  • Bazzichi L, Giacomelli C, Consensi A, Giorgi V, Batticciotto A, Di Franco M et al. One year in review 2020: fibromyalgia. Clin Exp Rheumatol. 2020;38:3-8.
  • Küçükşen S, Genç E, Yılmaz H, Sallı A, Gezer İA, Karahan AY et al. The prevalence of fibromyalgia and its relation with headache characteristics in episodic migraine. Clin Rheumatol. 2013;32:983-90.
  • Alles SRA, Smith PA. Etiology and pharmacology of neuropathic pain. Pharmacol Rev. 2018;70:315-47.
  • Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice ASC et al. A new definition of neuropathic pain. Pain. 2011;152:2204-05.
  • Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000;47:123-28.
  • Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, et al. Cytokine-induced sickness behavior. Brain Behav Immun. 2003;17:112-118.
  • Watkins LR, Maier SF. The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol. 2000;51:29-57.
  • Feng J, Zhang Z, Wu X, Mao A, Chang F, Deng X et al. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing. PLoS One. 2013;8:e65033.
  • Blanco I, Janciauskiene S, Nita I, Fernández-Bustillo E, Cárcaba V, Gallo C et al. Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia. Clin Rheumatol. 2010;29:189-97.
  • Mertoglu C, Gunay M, Yerligok O. Could endocan, a marker of inflammation and endothelial dysfunction, be a new diagnostic marker for fibromyalgia?. Clin Lab. 2018;64:405-10.
  • Nah SS, Lee H, Hong Y, Im J, Won H, Chang SH et al. Association between endothelin‑1 and fibromyalgia syndrome. Mol Med Rep. 2017;16:6234-39.
  • Sommer C. Zytokine bei neuropathischen Schmerzen [cytokines in neuropathic pain]. Anaesthesist. 2001;50:416-26.
  • Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319-29.
  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-71.
  • Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893-7.
  • Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 2001;92:147-57.
  • Schrödinger LLC. The PyMOL molecular graphics system. Version 2.5.2. 2010.
  • Rakhmetov A, Lee SP, Grebinyk D, Ostapchenko L, Chae HZ. Simulation of peroxiredoxin II and brain-type creatine Kinase protein-protein interaction using the on-line docking server ClusPro 2.0. J App Pharm Sci. 2015;5:011-016.
  • Kozakov D, Beglov D, Bohnuud T, Mottarella SE, Xia B, Hall DR et al. How good is automated protein docking? Proteins. 2013;81:2159-66.
  • Chuang GY, Kozakov D, Brenke R, Comeau SR, Vajda S. DARS (Decoys As the Reference State) potentials for protein-protein docking. Biophys J. 2008;95:4217-27.
  • Xue LC, Rodrigues JP, Kastritis PL, Bonvin AM, Vangone A. PRODIGY: a web server for predicting the binding affinity of protein-protein complexes. Bioinformatics. 2016;32:3676-78.
  • Vangone A, Bonvin AM. Contacts-based prediction of binding affinity in protein-protein complexes. Elife. 2015;4:e07454.
  • Valdés H, Díaz N, Suárez D, Fernández-Recio J. Interdomain Conformations in the full-length MMP-2 enzyme explored by protein-protein docking calculations using pyDock. J Chem Theory Comput. 2010;6:2204-13.
  • Kastritis PL, Bonvin AM. Are scoring functions in protein-protein docking ready to predict interactomes? Clues from a novel binding affinity benchmark [published correction appears in J Proteome Res 2011 Feb 4;10:921-2]. J Proteome Res. 2010;9:2216-25.
  • Mottin M, Souza PC, Skaf MS. Molecular recognition of PPARγ by kinase Cdk5/p25: insights from a combination of protein-protein docking and adaptive biasing force simulations. J Phys Chem B. 2015;119:8330-39.
  • Qiao B, Lopez L, Olvera de la Cruz M. "Mirror"-like protein dimers stabilized by local heterogeneity at protein surfaces. J Phys Chem B. 2019;123:3907-15.
  • Soulier JL, Russo O, Giner M, Rivail L, Berthouze M, Ongeri S et al. Design and synthesis of specific probes for human 5-HT4 receptor dimerization studies. J Med Chem. 2005;48:6220-28.
  • Koldsø H, Andersen OJ, Nikolajsen CL, Scavenius C, Sørensen CS, Underhaug J et al. Early events in the amyloid formation of the A546T mutant of transforming growth factor β-induced protein in corneal dystrophies compared to the nonfibrillating R555W and R555Q mutants. Biochemistry. 2015;54:5546-5556.
  • Kahler U, Kamenik AS, Waibl F, Kraml J, Liedl KR. Protein-protein binding as a two-step mechanism: preselection of encounter poses during the binding of BPTI and trypsin. Biophys J. 2020;119:652-66.
  • Cui W, Wei Z, Chen Q, Cheng Y, Geng L, Zhang J et al. Structure-based design of peptides against G3BP with cytotoxicity on tumor cells. J Chem Inf Model. 2010;50:380-87.
  • Yang Z, Bogdan P, Nazarian S. An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study. Sci Rep. 2021;11:3238.
  • Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Semin Immunopathol. 2018;40:291-300.
  • Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, et al. Age-related impairment of vascular structure and functions. Aging Dis. 2017;8:590-610.
  • Wang H, Moser M, Schiltenwolf M, Buchner M. Circulating cytokine levels compared to pain in patients with fibromyalgia - a prospective longitudinal study over 6 months. J Rheumatol. 2008;35:1366-70.
  • Ang DC, Moore MN, Hilligoss J, Tabbey R. MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study. Pain Med. 2011;12:1154-61.
  • Yoshio T, Masuyama J, Mimori A, Takeda A, Minota S, Kano S. Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. Ann Rheum Dis. 1995;54:361-65.
  • Pache M, Schwarz HA, Kaiser HJ, Wüest P, Klöti M, Dubler B, et al. Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis. Med Sci Monit. 2002;8:CR616-CR619.
  • Pache M, Ochs J, Genth E, Mierau R, Kube T, Flammer J. Increased plasma endothelin-1 levels in fibromyalgia syndrome. Rheumatology (Oxford). 2003;42:493-94.
  • Bauer V, Sotníková R. Nitric oxide--the endothelium-derived relaxing factor and its role in endothelial functions. Gen Physiol Biophys. 2010;29:319-40.
  • Cunningham ME, Huribal M, Bala RJ, McMillen MA. Endothelin-1 and endothelin-4 stimulate monocyte production of cytokines. Crit Care Med. 1997;25:958-64.
  • Hans G, Deseure K, Adriaensen H. Endothelin-1-induced pain and hyperalgesia: a review of pathophysiology, clinical manifestations and future therapeutic options. Neuropeptides. 2008;42:119-32.
  • Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549-80.
  • Delehedde M, Devenyns L, Maurage CA, Vivès RR. Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan. Int J Cell Biol. 2013;2013:705027.
  • Mahmoud EA, Moneim WA, Shaker OG, Ghalwash DM. Expression of endocan and vascular endothelial growth factor in recurrent minor aphthous ulcers. J Clin Exp Dent. 2019;11:e534-e541.
  • Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev. 2009;89:607-48.
  • Lin J, Li G, Den X, Xu C, Liu S, Gao Y et al. VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X₂(/)₃ receptor of primary sensory neurons. Brain Res Bull. 2010;83:284-91.
  • Lee HL, Oh J, Yun Y, Lee HY, You Y, Che L, et al. Vascular endothelial growth factor-expressing neural stem cell for the treatment of neuropathic pain. Neuroreport. 2015;26:399-404.
  • Lee GW, Son JY, Lee AR, Ju JS, Bae YC, Ahn DK. Central VEGF-A pathway plays a key role in the development of trigeminal neuropathic pain in rats. Mol Pain. 2019;15:1744806919872602.
  • Kim SK, Kim KS, Lee YS, Park SH, Choe JY. Arterial stiffness and proinflammatory cytokines in fibromyalgia syndrome. Clin Exp Rheumatol. 2010;28:S71-S77.
  • Tas A, Hayta E, Karadag A, Zontul C, Ozmen E, Aydin S, et al. Potassium ion channel protein (KCNH) levels in patients with fibromyalgia syndrome. Cell Mol Biol. 2022;67:451-57
Toplam 50 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma
Yazarlar

Özlem Balbaloğlu 0000-0003-2813-3406

Nihal İnandıklıoglu 0000-0001-7137-3929

Kayode Yomi Raheem 0000-0001-7975-9228

Proje Numarası 6602b-TF/19-301
Erken Görünüm Tarihi 10 Temmuz 2023
Yayımlanma Tarihi 2 Temmuz 2023
Kabul Tarihi 31 Mayıs 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 48 Sayı: 2

Kaynak Göster

MLA Balbaloğlu, Özlem vd. “The Relationship Between Neuropathic Pain and Serum Endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, VEGF-A Levels in Fibromyalgia Patients and Molecular Docking Results”. Cukurova Medical Journal, c. 48, sy. 2, 2023, ss. 522-34, doi:10.17826/cumj.1273163.
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