Clinical trial NCT03804034: Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response
Official title: Neurogenic Inflammation and Angiogenesis in the Human Dental Pulp in Response to Occlusal Interferences and Orthodontic Movements
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Occlusal Trauma
Orthodontic Appliance Complication
Keywords: Neurogenic inflammation
Dental Pulp
Occlusal trauma
Orthodontics forces
SP
CGRP
VEGF
Lead sponsor: Institucion Universitaria Colegios de Colombia
Sponsor class: OTHER
Collaborators: name: Universidad Cooperativa de Colombia seccional Pasto
First posted: 2019-01-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Human dental pulp was obtained from 40 freshly extracted maxillary and mandibular premolars with orthodontic indication from 20 healthy patients, both male and female, aged between 18 and 30 yearsThe premolars were randomly distributed into four groups, namely a group without occlusal trauma and orthodontic force chosen as the control group and three experimental groups, i.e., one occlusal trauma group experimentally induced by occlusal interferences, one moderate orthodontic force group, and one occlusal trauma plus moderate orthodontic force group.
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: SP expression (pmol/mg in pulp tissue)
timeFrame: 24 hours stimulations
Secondary outcomes:
measure: CGRP expression (pmol/mg in pulp tissue)
timeFrame: 24 hours stimulations
measure: VEGF expression (pmol/mg in pulp tissue)
timeFrame: 24 hours stimulations
Other outcomes:
Locations:
city: Bogota
country: Colombia
facility: Facultad de Odontologia, Unicoc
Study officials:
References:
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