Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response
Condition: Occlusal Trauma; Orthodontic Appliance Complication
MeSH terms: Neurogenic Inflammation; Inflammation
Study type: Interventional

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.
    

Intervention name(s): Block of resin; Buccal tube, Bracket and 0.0017 × 0.025 in titanium molybdenum alloy wire
Intervention type(s): Device; Device
Intervention MeSH terms: Molybdenum
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Neurogenic inflammation; Dental Pulp; Occlusal trauma; Orthodontics forces; SP; CGRP; VEGF