History of Endodontics aae/abe

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Pulpal Pathophysiology & Inflammation

Hydrodynamic Theory of Dentinal Sensitivity


  1. Heat causes inward fluid movement in tubules

  2. Cold causes outward fluid movement in tubules

  3. Concurrent distortion of odontoblastic process stimulates 1 neurons at the pulpo-dentinal junction.

  4. Distortion leads to impulse conduction

Pulpal Functions & Formation

  1. Functions: Induction, Formation, Nutrition, Defense, Sensation

  2. Development: Ectomesynchymal cells proliferate to form Dental papilla which gives rise to odontoblasts/dentin and pulpal tissues

A-delta and C-fibers

  1. Narhi -

    1. A delta fibers: Mechanoreceptors; respond to hydrodynamic stimuli (i.e.: cold, heat, air, hyper-osmotic sol; plexus of rashkow; dentinal pain

    2. C fibers: Polymodal nociceptors; respond to tissue injury, Capsaicin, prolonged heat, inflammatory mediators, acids; pulp proper; pulpal pain

  1. Johnsen 1983 -

    1. >2000 neural axons innervate human premolar

    2. 80% pulpal neurons are unmyelinated C fibers

    3. Myelinated A fibers are late to innervate pulp, may take up to 5 years (EPT unreliable in young teeth – see Fuss/Trowbridge, Fulling/Andreasen)

    4. Threshold stimulus level decreases significantly with apical closure

  1. Matthews 1994 -

    1. 90% of myelinated A fibers in dental pulp are A-delta fibers

Sympathetic & Parasympathetic Innervation

  1. Trowbridge 1986

    1. Sympathetic efferent fibers originating from the superior cervical ganglion

    2. Innervate smooth muscle cells of arterioles and precapillary sphincters

    3. Vasoconstriction and reduction of blood flow to the pulp

  1. Edwall 1985

    1. Sympathetic fibers derived from the superior cervical ganglion form plexuses around pulpal arterioles

    2. Responsible for constriction of arterioles/decrease in blood flow to pulp

    3. Sympathetic neural terminals contain NE and NPY

  1. Sassano 1995

    1. Absence of parasympathetic (VIP) vasodilation in the pulp

Dentinal Tubules & Odontoblastic Processes

  1. PashleyDiameter and density of tubules increases closer to the pulp:

    1. Density: DEJ – 18,000 tubules/mm2, Pulp – 45,000 tubules/mm2

    2. Diameter: DEJ – 0.8 m, Pulp – 2.5 m

    3. Occupied Space: DEJ – 1% surface area, Pulp – 22% surface area

  1. Byers – Intratubular A fibers extend into dentinal tubules as far as 100 m, most numberous in the pulp horns (40% tubules), least numerous in root dentin (1% tubules)

  1. Sigel – Odontoblastic process extends to DEJ

  1. Holland – Odontoblastic process extends ½ way through the tubule.

  1. Aubin – Odontoblastic process extends to DEJ

Trowbridge - Histopathology of foreign body reactions

Type I Anaphylactic - IgE mediated (Mast cells/Basophils  Histamine, C4 leukotrienes –  vasodilation/vascular permeability and bronchial smooth muscle contstriction), IMMEDIATE ie: drugs, foods, asthma, bites, allergic rhinitis
Type II Cytotoxic - IgG, IgM mediated (complement or phagocytosis)- Transfusion rxn, autoimmune hemolytic anemia, idiopathic thrombocytopenia

Type III Immune complex (Ag-Ab) rxnIgG form complexes w/ complement, 6-8 hrs, ie: serum sickness, arthus, immune vasiculitis, lupus, viral hepatitis
Type IV Delayed Hypersensitivity rxn - Cell mediated (no Ab): T cell (Killer T cells, Memory T cells), Macrophages; antigen sensitized T cells/Macrophages. More important than anaphylaxis rxn. 24-48 hours DELAYED

ie: 48 hours contact dermatitis, poison ivy

tissue graft rejection, TB, autoimmune diseases

Granulomatous Inflammation (i.e.: Periapical granuloma)

What Immune cells are found in the Healthy Pulp?
Jontell/Bergenholtz 1998

  1. T-lymphoctyes (CD4+ and CD8+): B cell/Macrophage activation, mem.

  2. Macrophages: Phagocytosis, APC

  3. Dendritic Cells: APC, phagocytosis; Perivascular/Periodontoblastic

  4. Lack of B-lymphocytes, Mast cells from healthy pulps (see Suda)

Soh - Dendritic Cells present in pulp
ByersFibroblasts are most numerous cell in pulp and produce NGF and proinflammatory cytokines during inflammation
Hahn – T lymphocytes in normal pulp, T suppressor most predominant
Suda – Mast Cells are NOT present in normal pulps
Pulpal Changes as related to depth of bacteria

  1. Baum – Found correlation between depth of penetration of bacteria within dentin and severity of inflammation

  2. Brannstrom/Lind – Pulpal changes occur early in caries, even in incipient lesions. Impairment of odontoblast layer, accumulation of lymphocytes

  3. Reeves & StanleyIrreversible pulpitis detected when bacteria were 0.5mm from the pulp, little pathosis seen if >1.2 mm from pulp. If bacteria invade repairative dentin = irreversible pulpitis.

  4. Stanley – Rate of repairative dentin formation = 1.49 micrometers/day, tertiary dentin begins 19 days after operative procedures.

  5. Seltzer/Bender (classic) – Described classic caries progression to pulp

  6. Jontell/Bergenholtz – Macrophages/Dendritic cells (APCs) initiate pulpal response to caries. T lymphocytes present. B lymphocytes/mast cells later arrivals. Multiple immune responses: Antigen-Ab IgG (III), Delayed type Hypersensitivity w/T cell/Macrophages (IV), Vascular and Neurogenic interactions.

Pulpal Reactions to Caries (See Baum, Reeves/Stanley, Branstromm/Lind)
Shallow - Moderate caries:

  1. 1st defense: Sclerotic dentin (crystals) deposition, dentin permeability

  2. 2nd defense: Tertiary dentin formation, Mild stimuli – Reactionary dentin, Aggressive stimuli (death of odontoblast) – Reparative dentin

  3. 3rd defense: Immune response

    1. Chronic inflammatory response –Initially Odontoblasts, later dendritic cells as most peripheral cells contain PRRs to respond to PAMPs with innate/adaptive immune response

    2. Release of Cytokines, Chemokinesphagocytosis, chemotaxis, recruitment of lymphocytes, macrophages, and plasma cells

    3. Neurogenic inflammationSP, CGRP, NKA released from pulpal nociceptors (PRRs – TLRs on nociceptors)

Deep caries:

  1. Acute excerbation of chronic inflammatory response – Influx of PMNs

  2. Localized inflammation, Focal Microabscesses, Progressive necrosis

Inflammation: PAMPs & PRRs

Initiation of host response – Innate Immunity

PAMP = Pathogen Associated Molecular Pattern (ie: LPS, LTA, Peptidoglycan)

PRR = Pattern Recognition Receptor (ie: Toll Like Receptors (TLRs), CD-14)
Wadachi/Hargreaves 2006 – TRPV1 (Capsaicin) C fiber nociceptors express TLR-4 and CD-14, subclasses of Pattern Recognition Receptors able to sense bacterial presence through PAMPs (i.e.: LPS), and able to directly activate these nociceptors or influence their release of Neuropeptides
Farges 2008Odontoblast TLR-2 stimulation by bacterial PAMP results in release of proinflammatory cytokines, chemokines, other mediators
Horst 2007Odontoblasts contain TLR 2, TLR 8

Jiang 2006Odontoblasts, Pulpal vascular endothelial cells contain TLR4
Farges 2010 – Dendritic cells TLR-2 stimulation by LTA (PAMP)

Pathogen Associated Molecular Patterns (PAMPs)

  1. Dickerson 1998 - LPS activation of pulpal nociceptors – SP/CGRP release (TLR-4)

  2. Akira 2001 - LPS stimulation of TLRs (PRRs) on Dendritic cells


  1. Farges 2013LTA activation of TLR2 on pulpal odontoblasts stimulates pro-inflammatory cytokine release

  2. Farges 2010 – LTA activation of TLR2 on Dendritic cells stimulates production of TNF-, IL-1, and IL-8


  1. Adachi 2007 – Peptidoglycan promotes chemokine production by pulpal fibroblasts

Acute Inflammation (Innate Immunity)

1st 24 hrs

  1. PAMPs bind PRRs (TLRs, CD14) on resident immune cells (dendritic cells, macrophages), odontoblasts, and peripheral nociceptors (TRPV1 C fibers)

  2. Pro-inflammatory cytokines (i.e.: IL-1, IL-6, IL-8, TNF-) and neuropeptides (CGRP, SP, NKA) are released to activate/recruit immune cells as well as sensitize/activate nociceptors,  nerve sprouting, and effect vasodilatory responses

  3. Complement activation via cytokines and neuropeptides  releasing C3a, C5a  vascular endothelium for chemotaxis, opsonization and killing of foreign antigens

24hrs +

  1. Cytokines (i.e.: IL-1, TNF-) & C3a/C5a effect endothelial cells for chemotaxis and migration of PMNs, Bradykinin, other pro-inflammatory cells

  2. C3a/C5a & neuropeptides (SP, CGRP) activate mast cells to produce Histamine, Leukotrienes, Platelet Activating Factor (Vasodilation,  Vascular Permeability)

  3. Sensitization/Activation of Nociceptors  Hyperalgesia, Allodynia, Spont. pain

  4. Vasodilation, Vascular Permeability  Edema, Inc. Tissue pressure

  5. Non-specific phagocytosisPMNs (0-48hrs), Macrophages (48 hrs +)

  6. Cytokines effect Osteoclasts to promote RANK/RANKL binding and bone resorption

Chronic Inflammation (Adaptive Immunity)
2 Components of Adaptive Immune Response (48 hrs +):

  1. Humoral Immune ResponseAntibody mediated response

  2. Cellular Immune Response – T cell mediated response – CD4+ T cells

  1. Antigen presenting cells (APCs), i.e.: Macrophages, Dendritic cells, B cells, present to immature TH0 cells within lymph nodes via MHC II receptor, activating TH0 cells

  2. TH0 cells differentiate into TH1or TH2 cells via cytokine regulation: TH1 via IFN-, TH2 via IL-4, IL-10 (suppresses IFN- and TH1 production)

  3. Cellular Immune Response: TH1  Maximizes killing by Macrophages, CD8+ cells (NKT cells, Cytotoxic T cells), Memory T cell production

  4. Humoral Immune Response: TH2  B cell activation  Plasma Cells  Antibody production (allows binding to antigen for complement killing or phagocytosis), Memory B cell production

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