Scopus (CiteScore 2022 =3.0, Q3) , ISC

Document Type : Original Research Article

Authors

1 Department of Conservative Dentistry, Faculty of Dentistry Airlangga University, Surabaya, Indonesia

2 Conservative Dentistry Specialist Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia

3 Undergraduate Program, Faculty of Dentistry Airlangga University, Surabaya, Indonesia

10.48309/ecc.2024.426101.1739

Abstract

An inflammatory cytokine called tumor necrosis factor alpha (TNFα) is responsible for coordinating the body's reaction to injury and illness. TNFα expression can cause nociceptors to become hypersensitive to pain in addition to promoting inflammation. Based on a neuroimmunological approach, the immunohistochemistry image was examined by looking at the expression of TNFα and Hsp10 in macrophages and voltage-gated sodium channel 1.7 (Nav1.7) in nerve cells. Fifteen Sprague Dawley mice were used in the laboratory experiment; the animals were split into three groups, each with five mice: a control group, a group that removed normal pulp tissue, and a group that removed inflammatory pulp tissue. Tissue samples were taken from dental apical field of the mandibular incisor. The samples were all analyzed by immunohistochemistry techniques. When compared to the normal pulp tissue extraction group, the inflamed pulp tissue extraction group revealed a substantial drop in Nav1.7 expression, suggesting that Nav1.7 expression can be disrupted by increased Hsp10 expression. It implies that the discomfort risk during pulp extraction surgery will be reduced if the tooth pulp is infected or inflamed. The pulp tissue experiences an upregulation of TNFα expression upon extraction. Pain is caused by an increase in TNFα expression, which also raises Nav1.7 expression via the TNFR pathway. In the meantime, removing inflammatory pulp tissue significantly increases Hsp10 expression, which results in a drop in TNFα and Nav1.7 expression. When normal pulp tissue is removed, the pain response is more intense than when infected or inflammatory pulp tissue is removed.

Graphical Abstract

Expression of tnfα, hsp10, and nav1.7 in normal and inflamed dental pulp after pulp tissue extirpation

Keywords

Main Subjects

  1. [1] a) L. M. Lin, D. Ricucci, T. M. Saoud, A. Sigurdsson, B. Kahler, Vital Pulp Therapy of Mature Permanent Teeth With Irreversible Pulpitis From The Perspective of Pulp Biology, Australian Endodontic Journal, 2020, 46, 154–166. [Crossref], [Google Scholar], [Publisher], b) H.M. Bidhendi, Use chemical materials in automatic segmentation of teeth using X-ray, Advanced Journal of Chemistry-Section B: Natural Products and Medical Chemistry, 2023, 5, 1-13. [Crossref], [Google Scholar], [Publisher]

    [2] D. Sadaf, Success of coronal pulpotomy in permanent teeth with irreversible pulpitis: an evidence-based review, Cureus, 2020, 12, 23–27. [Crossref], [Google Scholar], [Publisher]

    [3] S. Tabassum, F.R. Khan, Failure of endodontic treatment: The usual suspects, European journal of dentistry, 2016, 1,144–147. [Crossref], [Google Scholar], [Publisher]

    [4] S. Bassam, R. El-Ahmar, S. Salloum, S. Ayoub, Endodontic postoperative flare-up: An update, The Saudi dental journal, 2021, 33, 7, 86-394. [Crossref], [Google Scholar], [Publisher]

    [5] K.A. Lakshmi, G. U. Rao, M. Jayaraman, A. Ramdhas, Endodontic Flare-ups: A review, RGUHS Journal of Medical Sciences, 2020, 10, 9-17. [Crossref], [Google Scholar], [Publisher]

    [6] J. Hegde, V. Prakash, R. Gupta, A. Srirekha, Concise conservative dentistry and Endodontics-E book, Elsevier Health Sciences, 2019, 628. [Google Scholar], [Publisher]

    [7] O. Özdemir, Postoperative Pain in Endodontics, On J Dent & Oral Health, 2020, 3, 1-4.  [Crossref], [Google Scholar], [Publisher]

    [8] C. Aoun, N. El Costa, A. Naaman, C. Zogheib, I. Khalil, Post-endodontic flare-ups after a single-visit treatment using the FUI scoring method and associated factors: a clinical prospective study, Journal of Contemporary Dental Practice, 2019, 20, 1033–1040. [Google Scholar], [Publisher]

    [9] J.P. Vieyra, F.J.J. Enriquez, F.O. Acosta, J.A. Guardado, Reduction of postendodontic pain after one-visit root canal treatment using three irrigating regimens with different temperature, Nigerian journal of clinical practice, 2019, 22, 34–40. [Crossref], [Google Scholar], [Publisher]

    [10] A. Brodzikowska, M. Ciechanowska, M Kopka, A. Stachura, P.K. Włodarski, Role of lipopolysaccharide, derived from various bacterial species, in pulpitis-A systematic review, Biomolecules, 2022, 12, 138. [Crossref], [Google Scholar], [Publisher]

    [11] M.M. Tucureanu, D. Rebleanu, C.A. Constantinescu, M. Deleanu, G. Voicu, E. Butoi, M. Calin, I. Manduteanu, Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor, International Journal of Nanomedicine, 2017, 20, 63-76. [Crossref], [Google Scholar], [Publisher]

    [12] S. Zhao, J. Jiang, Y. Jing, W. Liu, X. Yang, X. Hou, L. Gao, L. Wei, The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity, Cell death & disease, 2020, 11,  1-13. [Crossref], [Google Scholar], [Publisher]

    [13] M.S. Saddala, H. Huang, Identification of novel inhibitors for TNFα, TNFR1 and TNFα-TNFR1 complex using pharmacophore-based approaches, Journal of translational medicine,   2019, 17, 215. [Crossref], [Google Scholar], [Publisher]

    [14] E. Varvolomeev, D. Vucic, Intracellular regulation of TNF activity in health and disease, Cytokine, 2018, 101, 26-32. [Crossref], [Google Scholar], [Publisher]

    [15] P. Gough, I.A. Myles, Tumor necrosis factor receptors: pleiotropic signaling complexes and their differential effects, Frontiers in immunology2020, 11,585880. [Crossref], [Google Scholar], [Publisher]

    [16] B.E. Hall, L. Zhang, S.J. Sun, E. Utreras, M. Prochazkova, A. Cho, A. Terse, P. Arany, J.C. Dolan, B.C. Schmidt, A.B. Kulkarni, Conditional TNF-α overexpression in the tooth and alveolar bone results in painful pulpitis and osteitis, Journal of dental research,   2016, 95, 188–195. [Crossref], [Google Scholar], [Publisher]

    [17] Y. Huang, Y. Zang, L. Zhou, W. Gui, Y. Zgong, The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1. 7 in DRG neurons of rats with diabetic neuropathy, Neurochemistry International,   2014, 75, 112-119. [Crossref], [Google Scholar], [Publisher]

    [18] S. Corrao, C. Campanella, R. Anzalone, F. Farina, G. Zummo, E. Conway de Macario, A.J. Macario, F. Cappello, G. La Rocca, Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives, Life sciences, 2010, 86, 145-152. [Crossref], [Google Scholar], [Publisher]

    [19] T. Zininga, L. Ramatsui, A. Shonhai, Heat shock proteins as immunomodulants, Molecules 2018, 23, 2846. [Crossref], [Google Scholar], [Publisher]

    [20] A.A. Azim, K.A. Azim, P.V. Abbott, Prevalence of inter-appointment endodontic flare-ups and host-related factors, Clinical oral investigations, 2017, 21, 889–894. [Crossref], [Google Scholar], [Publisher]

    [21] M. Gotler, G.B. Bar, M. Ashkenazi, Postoperative pain after root canal treatment: a prospective cohort study, International journal of dentistry, 2012, 310467. [Crossref], [Google Scholar], [Publisher]

    [22] S. Elge, M. Rasmute, Pain and flare-up after endodontic treatment procedures, Stomatologija, 2014, 16, 25-30. [Google Scholar], [Publisher]

    [23] M. Nair, J. Rahul, A. Devadathan, J. Mathew, Incidence of endodontic flare ups and its related factors: A retrospective study, Journal of Internasional Society of Preventive and Community Dentistry, 2017, 7, 175-

    1. [Crossref], [Google Scholar], [Publisher]

    [24] J. Shao, J. Cao, J. Wang, X. Ren, S. Su, M. Li, Z. Li, Q. Zhao, W. Zang, MicroRNA-30b regulates expression of the sodium channel Nav1. 7 in nerve injury-induced neuropathic pain in the rat, Molecular pain,  2016, 12, 1744806916671523. [Crossref], [Google Scholar], [Publisher]

    [25] G. Sampoerno, J. Sunariani, Kuntaman, Expression of NaV-1.7, TNF-α and HSP-70 in experimental flare-up post-extirpated dental pulp tissue through a neuroimmunological approach, The Saudi Dental Journal, 2020, 32, 206-218. [Crossref], [Google Scholar], [Publisher]

    [26] Kim So-Woon, Park Jin Roh Chan-Sik. Immunohistochemistry for pathologists: protocols, pitfalls, and tips, Journal of pathology and translational medicine, 2016, 50, 411-419. [Crossref], [Google Scholar], [Publisher]

    [27] G. Sampoerno, A. Bhardwaj, P.Y. Divina, N.N. Fripertiwi, N.H. Adipradana, Neurogenic Inflammation pathway on the up-regulation of voltage-gated sodium channel NaV1. 7 in experimental flare-up post-dental pulp tissue Extirpation, Journal of International Dental and Medical Research, 2022, 15, 124-130. [Google Scholar], [Publisher]

    [28] S. Tukaj, Heat shock protein 70 as a double agent acting inside and outside the cell: insights into autoimmunity, International Journal of Molecular Sciences, 2020, 21, 5298. [Crossref], [Google Scholar], [Publisher]

    [29] W. Chen, J. Sheng, J. Guo, F. Gao, X. Zhao, J. Dai, Tumor necrosis factor-α enhances voltage-gated Na+ currents in primary culture of mouse cortical neurons, Journal of neuroinflammation,  2015, 12, 1-10. [Crossref], [Google Scholar], [Publisher]

    [30] F.H.P. Macedo, R.D. Aires, E.G. Fonseca, R.C.M. Ferreira, D.P.D. Machado, L. Chen, F.X. Zhang, I.A. Souza, V.S. Lemos, T.R.L. Romero, A. Moutal, R. Khanna, G.W. Zamponi, J.S. Cruz, TNF-α mediated upregulation of Na V 1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation, Molecular brain,  2019, 12, 1-14. [Crossref], [Google Scholar], [Publisher]

    [31] R. Tamura, T. Nemoto, T. Maruta, S. Onizuka, T. Yanagita, A. Wada, I. Tsuneyoshi, Up-regulation of NaV1. 7 sodium channels expression by tumor necrosis factor-α in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons, Anesthesia & Analgesia, 2014, 118, 318–324. [Crossref], [Google Scholar], [Publisher]

    [32] M.X. Xie, X.L. Zhang, J. Xu, W.A. Zeng, D. Li, T. Xu, R.P. Pang, K. Ma, X.G. Liu, Nuclear factor-kappaB gates Nav1. 7 channels in DRG neurons via protein-protein interaction, Iscience,   2019, 19, 623–633. [Google Scholar], [Publisher]

    [33] L. Klapal, B.A. Igelhorst, I.D. Dietzel-Meyer, Changes in neuronal excitability by activated microglia: differential Na+ current upregulation in pyramid-shaped and bipolar neurons by TNF-α and IL-18, Frontiers in Neurology,   2016, 7, 44. [Crossref], [Google Scholar], [Publisher]

    [34] M. Leo, S. Argalski, M. Schäfers, T. Hagenacker, Modulation of voltage-gated sodium channels by activation of tumor necrosis factor receptor-1 and receptor-2 in small DRG neurons of rats, Mediators of Inflammation,  2015, 124942. [Crossref], [Google Scholar], [Publisher]

    [35] A.M. Shields, G.S. Panayi, V.M. Corrigall, Resolution-associated molecular patterns (RAMP): RAMParts defending immunological homeostasis?. Clinical & Experimental Immunology, 2011, 165, 292-300. [Crossref], [Google Scholar], [Publisher]

    [36] A. Mázló, Y. Tang, V. Jenei, J. Brauman, H. Yousef, A. Bácsi, G. Koncz,  Resolution Potential of Necrotic Cell Death Pathways, International Journal of Molecular Sciences,   2022, 24, 1, 16. [Crossref], [Google Scholar], [Publisher]

    [37] B. Zhang, M.D. Walsh, K.B. Nguyen, N.C. Hillyard, A.C. Cavanagh, P.A. McCombe, H. Morton, Early pregnancy factor treatment suppresses the inflammatory response and adhesion molecule expression in the spinal cord of SJL/J mice with experimental autoimmune encephalomyelitis and the delayed-type hypersensitivity reaction to trinitrochlorobenzene in normal BALB/c mice, Journal of the neurological sciences, 2003, 212, 37-46. [Crossref], [Google Scholar], [Publisher]

    [38] B.J. Johnson, T.T. Le, C.A. Dobbin, T. Banovic, C.B. Howard, M. Flores Fde, D. Vanags, D.J. Naylor, G.R.  Hill, A. Suhrbier, Heat shock protein 10 inhibits lipopolysaccharide-induced inflammatory mediator production, Journal of Biological Chemistry, 2005, 280, 4037-4084. [Crossref], [Google Scholar], [Publisher]

    [39] H. Wajant, D. Siegmund, TNFR1 and TNFR2 in the control of the life and death balance of macrophages, Frontiers in cell and developmental biology, 2019, 7, 91. [Crossref], [Google Scholar], [Publisher]

    [40] S.F. Josephs, T.E. Ichim, S.M. Prince, S. Kesari, F.M. Marincola, A.R. Escobedo, A. Jafri, Unleashing endogenous TNF-alpha as a cancer immunotherapeutic, Journal of translational medicine, 2018, 16,   242. [Crossref], [Google Scholar], [Publisher]