Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response

Orthodontic Appliance Complication Clinical Trial

Official title:

Neurogenic Inflammation and Angiogenesis in the Human Dental Pulp in Response to Occlusal Interferences and Orthodontic Movements

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03804034
• Other study ID #: JCB002
• Status: Completed
• Phase: N/A
• Start date: July 2, 2013
• Est. completion date: January 12, 2015

Study information

• Verified date: April 2019
• Source: Institucion Universitaria Colegios de Colombia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study measures SP, CGRP and VEGF expression in human dental pulp under occlusal trauma induced by occlusal interferences under moderate orthodontic forces or under a combination of occlusal trauma and moderate orthodontic forces because in clinical reality, patients under orthodontic treatment experience a combination of these stimuli on their pulp tissue.

Description:

Substance P (SP) and calcitonin gene-related peptide (CGRP) are neuropeptides that are assembled in the cell bodies of the trigeminal nerve and are transported through axonal flow to the nerve endings in human dental pulp, mainly in type-C nerve fibers and free nerve endings, where they are released to fulfill important biological functions.

SP plays an important role in pulp tissue reparation because it stimulates angiogenesis using direct mechanisms by modulating the growth of endothelial cells and fibroblasts through the activation of growth factors such as VEGF and IGF-1 and stimulates cell migration and proliferation to form mineralized tissue as a defense mechanism. It also uses indirect mechanisms such as binding to granulocytes or macrophages, which allow cells with angiogenic potential to be attracted.

CGRP has a key role in pulp reparation because of its angiogenic potential, which is linked to endothelial cell stimulation via the cAMP-PKA pathway, promoting cell proliferation. It boosts VEGF expression and stimulates focal adhesion kinase involved in the stabilization and maturation of blood vessels. It can stimulate growth factors that act on fibroblasts, such as HGF, IGF-1, and bFGF, and it can also produce an effect on odontoblast-like cells by increasing BMP-2 expression and allowing cell proliferation after 24 h. This shows that it can contribute to mineralized matrix formation

Angiogenesis is mediated by several growth factors, such as the VEGF. VEGF is released in the pulp tissue as a response to a harmful stimulus to counteract emerging hypoxic areas regulating oxygen and nutrients supply to cell populations by forming new blood vessels. VEGF is present in endothelial cells, mast cells, macrophages, lymphocytes, undifferentiated mesenchymal cells, fibroblasts, and odontoblast-like cells, and it controls neurogenic inflammation and reparation processes in combination with SP due to its angiogenic potential.

SP, CGRP, VEGF expression can be altered by the masticatory function, occlusal trauma, orthodontic movements, or a combination of occlusal trauma and orthodontic movements, which often takes place in patients under orthodontic treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 12, 2015
• Est. primary completion date: January 27, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Teeth in normal masticatory function

• Complete root development verified clinically and radiographically

Exclusion Criteria:

• Patients under medication

• Smokers

• Pregnant women were excluded

• Teeth with caries

• Teeth with restaurations,

• Teeth with previous orthodontic treatment

• Teeth with periodontal disorders

• Teeth with parafunctional habits.

Related Conditions & MeSH terms

• Inflammation
• Neurogenic Inflammation
• Occlusal Trauma
• Orthodontic Appliance Complication

Intervention

Device:
• Block of resin

• Buccal tube, Bracket and 0.0017 × 0.025 in titanium molybdenum alloy wire

Locations

Country	Name	City	State
Colombia	Facultad de Odontologia, Unicoc	Bogota

Sponsors (2)

Lead Sponsor	Collaborator
Institucion Universitaria Colegios de Colombia	Universidad Cooperativa de Colombia seccional Pasto

Country where clinical trial is conducted

Colombia, 

References & Publications (9)

Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG. Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. Int Endod J. 2002 Jan;35(1):30-6. — View Citation

Benemei S, Nicoletti P, Capone JG, Geppetti P. CGRP receptors in the control of pain and inflammation. Curr Opin Pharmacol. 2009 Feb;9(1):9-14. doi: 10.1016/j.coph.2008.12.007. Epub 2009 Jan 20. Review. — View Citation

Caviedes-Bucheli J, Arenas N, Guiza O, Moncada NA, Moreno GC, Diaz E, Munoz HR. Calcitonin gene-related peptide receptor expression in healthy and inflamed human pulp tissue. Int Endod J. 2005 Oct;38(10):712-7. — View Citation

Caviedes-Bucheli J, Azuero-Holguin MM, Correa-Ortiz JA, Aguilar-Mora MV, Pedroza-Flores JD, Ulate E, Lombana N, Munoz HR. Effect of experimentally induced occlusal trauma on substance p expression in human dental pulp and periodontal ligament. J Endod. 2011 May;37(5):627-30. doi: 10.1016/j.joen.2011.02.013. — View Citation

Caviedes-Bucheli J, Gomez-Sosa JF, Azuero-Holguin MM, Ormeño-Gomez M, Pinto-Pascual V, Munoz HR. Angiogenic mechanisms of human dental pulp and their relationship with substance P expression in response to occlusal trauma. Int Endod J. 2017 Apr;50(4):339-351. doi: 10.1111/iej.12627. Epub 2016 Apr 2. Review. — View Citation

Caviedes-Bucheli J, Lombana N, Azuero-Holguín MM, Munoz HR. Quantification of neuropeptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal polypeptide) expressed in healthy and inflamed human dental pulp. Int Endod J. 2006 May;39(5):394-400. — View Citation

Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell. 2011 Sep 16;146(6):873-87. doi: 10.1016/j.cell.2011.08.039. Review. — View Citation

Saghiri MA, Asatourian A, Sorenson CM, Sheibani N. Role of angiogenesis in endodontics: contributions of stem cells and proangiogenic and antiangiogenic factors to dental pulp regeneration. J Endod. 2015 Jun;41(6):797-803. doi: 10.1016/j.joen.2014.12.019. Epub 2015 Jan 31. Review. — View Citation

Wei F, Yang S, Xu H, Guo Q, Li Q, Hu L, Liu D, Wang C. Expression and Function of Hypoxia Inducible Factor-1a and Vascular Endothelial Growth Factor in Pulp Tissue of Teeth under Orthodontic Movement. Mediators Inflamm. 2015;2015:215761. doi: 10.1155/2015/215761. Epub 2015 Sep 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SP expression (pmol/mg in pulp tissue)	Sample Collection: All the teeth involved in this study were anesthetized and extracted 5 min after anesthetic application with conventional methods. Immediately after extraction, teeth were sectioned. Pulp tissue was obtained using a sterile endodontic excavator, placed on an Eppendorf tube, snap frozen in liquid nitrogen until the radioimmunoassay (RIA) test was performed.; Results are presented as SP expression in pmol/mg of pulp tissue. Means and standard deviations as well as minimum and maximum values for each neuropeptide were calculated.	24 hours stimulations
Secondary	CGRP expression (pmol/mg in pulp tissue)	Sample Collection: All the teeth involved in this study were anesthetized and extracted 5 min after anesthetic application with conventional methods. Immediately after extraction, teeth were sectioned. Pulp tissue was obtained using a sterile endodontic excavator, placed on an Eppendorf tube, snap frozen in liquid nitrogen until the radioimmunoassay (RIA) test was performed.; Results are presented as CGRP expression in pmol/mg of pulp tissue. Means and standard deviations as well as minimum and maximum values for each neuropeptide were calculated.	24 hours stimulations
Secondary	VEGF expression (pmol/mg in pulp tissue)	Sample Collection: All the teeth involved in this study were anesthetized and extracted 5 min after anesthetic application with conventional methods. Immediately after extraction, teeth were sectioned. Pulp tissue was obtained using a sterile endodontic excavator, placed on an Eppendorf tube, snap frozen in liquid nitrogen until the radioimmunoassay (RIA) test was performed.; Results are presented as CGRP expression in pmol/mg of pulp tissue. Means and standard deviations as well as minimum and maximum values for each growth factor were calculated.	24 hours stimulations