Pulpal Pathogenesis Caroline G. Ayoub

Outline  Contents of the healthy pulp  Etiology of pulpal disease  Immunological shift from health to disease  Take home points

What’s in the pulp?  Cells of pulp:  Odontoblasts  Fibroblasts  PMNs  Lymphocytes  Macrophages  Dendritic Cells – pulp, PDL, PA lesion  Mast Cells (chronic inflamed pulp only)  Other:  Ground substance  Blood vessels  Nerves

Odontoblast Dentin formation Main source of TGF-b Innate Immunity

Fibroblast Most numerous cells of the pulp Abundant in the cell-rich zone Synthesize types I and III collagen Have capacity to produce pro-inflammatory cytokines in response to PAMPs.

Immunocompetent Cells Lymphocytes  T lymphocytes: normal residents of human dental pulp  CD8+ outnumber CD4+ T lymphocytes in the dental pulp Macrophages  Primary function: Phagocytosis  Antigen presentation via expression of Cl II MHC molecules on their surface Dendritic Cells  Peculiar dendritic morphology  High motility  Limited phagocytic activity  Expression of high amounts of Cl II MHC molecules  Potent capacity for antigen presentation to T lymphocytes

Nerves PAIN A delta fibers C fibers Secondary dentin Dental pulp is among the most densely innervated tissues in the body

Etiology  Bacteria  Trauma  Orthodontic Tx

A schematic illustration of dental pulp responses to dental caries from Japanese Dental Science ReviewJapanese Dental Science Review Health to Disease

How do pulp cells react to the insult?  Odontoblasts: Host defense activated  Fibroblasts: Inflammatory mediators produced  Macrophages: APC  Dendritic Cells: APC  Lymphocytes: T cells recognize MHC on APC

In other words…

What about the Nerves?

Neuropeptides  The largest class of neurotransmitters/neuromodulators  Possess multiple recognition sites for receptor binding  Cannot cross cell membranes: Target cells need to have receptors and binding sites  Examples include:  Substance P (SP)  Calcitonin Gene-Related Peptide (CGRP)

Substance P  In the central pulp, SP fibers traverse in close proximity to blood vessels. In the periphery, many SP fibers are directly associated with small blood vessels  SP fibers are also observed at the subodontoblast layer where they branch toward predentin, with some SP fibers penetrating into the dentin

CGRP  Branch extensively in the coronal pulp near the pulp horn tip and enter into dentin for up to 0.1 mm  Multiple studies have demonstrated that trigeminal afferent neurons expressing CGRP innervate dental pulp  The existence of high-affinity binding sites for CGRP has been reported in the dental pulp as well as other tissues in the body.

So… Two dynamic changes occur to afferent neurons during inflammation: 1 st there is a sprouting of afferent fibers 2 nd local increases in inflammatory mediators trigger neuropeptide release Neurogenic inflammation

Take Home Points Innate Immunity Adaptive Immunity Neurogenic Inflammation