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

April 24, 2019 updated by: Javier Caviedes-Bucheli, Institucion Universitaria Colegios de Colombia

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Colombia
      • Bogota, Colombia
        • Facultad de Odontologia, Unicoc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 30 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Occlusal trauma group
an occlusal interference was placed on the lower teeth as follows. Articulating paper was used to mark the contact area between the upper and lower premolars indicated for extraction. Once established, the marked area on the lower premolar was acid-etched with 37% phosphoric acid for 15 s, washed, and dried. A bonding agent was placed and light-cured for 15 s, and finally, a 1- to 2-mm block of resin was placed over the contact area and light-cured for 40 s. Articulating paper was used again to verify that only the premolars that were going to be extracted had contact during normal occlusion as well as in lateral movements. Patients were given chewing gum and indications to repeat 20 masticatory cycles for 30 s, followed by a 30-s rest interval, and repeat the sequence again for a period of 30 min. This chewing cycle was repeated three times every 8 h for the first 24 h
Device: Block of resin
Experimental: Moderate orthodontic force group
A convertible standard buccal tube was bonded over the buccal face of the first molar with resin and a McLaughlin, Bennett, and Trevisi slot size 0.022 bracket was bonded over the buccal face of the premolars. One 0.0017 × 0.025 in titanium molybdenum alloy wire cantilever was inserted into each first molar tube, and the wire was bent buccally to form a helix. The cantilever was clinched to the distal end of the tube, and a tipping and extrusive force was applied on the premolar. The activation angle was 45° with a force of 56 g, which was applied to the tooth for 24 h before it was extracted.
Device: Buccal tube, Bracket and 0.0017 × 0.025 in titanium molybdenum alloy wire
Experimental: Occlusal trauma and moderate orthodontic force group
the combination of occlusal trauma and orthodontic force .
Device: Block of resin
Device: Buccal tube, Bracket and 0.0017 × 0.025 in titanium molybdenum alloy wire
No Intervention: Control Group
No experimental device to produce occlusal trauma or orthodontic forces

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SP expression (pmol/mg in pulp tissue)
Time Frame: 24 hours stimulations

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
CGRP expression (pmol/mg in pulp tissue)
Time Frame: 24 hours stimulations

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
VEGF expression (pmol/mg in pulp tissue)
Time Frame: 24 hours stimulations

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institucion Universitaria Colegios de Colombia

Collaborators

Universidad Cooperativa de Colombia seccional Pasto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 2, 2013

Primary Completion (Actual)

January 27, 2014

Study Completion (Actual)

January 12, 2015

Study Registration Dates

First Submitted

January 8, 2019

First Submitted That Met QC Criteria

January 14, 2019

First Posted (Actual)

January 15, 2019

Study Record Updates

Last Update Posted (Actual)

April 26, 2019

Last Update Submitted That Met QC Criteria

April 24, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JCB002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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