Pulp tissue circulation and innervation

The highest density of vessels is in the most coronal part of the pulp. The arteries enter the pulp through the apex and leave the pulp as venules. A dense network of capillaries supplies the odontoblasts, as well as all other interstitial cells, with nutrients and oxygen.

The existence of lymphatic vessels in the pulp has been debated for many years, and such lymphatic vessels were previously thought to contribute to fluid volume control and drainage in the tissue [6]. More recent studies shows that the dental pulp lacks lymphatic vessels (7,8).

The pulp is equipped with a high number of axons, both myelinated and unmyelinated. The majority (approximately 90%) is sensory nerve fibers and the rest is of autonomic character. The myelinated nerve fibers are of sensory origin and separated in Aβand Að fibers. Under normal conditions they have a lower threshold than unmyelinated sensory C-fibers (table 1). The fibers are activated by different stimuli and evoke either “prepain” or pain perception.

Both sensory and sympathetic nerve fibers accompany blood vessels and encircle them. While the sensory nerves emit a few branches in the radicular pulp, they branch extensively in the coronal pulp and form a subodontoblastic plexus. Some branches enter the dentinal tubules and reach the inner part of dentin (figure 2), especially under the cusps where also the tubule density is highest [9]. This may relate to the sensing of external irritation [10]. The nerve fibers are in intimate contact with odontoblasts and there may exist bidirectional communication [11].

Vascular responses and fluid transport

Inflammation in the pulp takes place in a low compliant environment, between rigid dentinal walls. The acute vascular reactions to an inflammatory stimulus are vasodilatation and increase in interstitial fluid volume due to increased vascular permeability, leading to a relatively large increase in the hydrostatic pressure in the pulp [12]. If the inflammatory response is spatially limited, fluid absorption occurs into nearby blood vessels [12] or by transportation toward non-inflamed lower pressure areas probably in loose connective tissue gaps toward apex [6] (figure 3). The drainage capacity can explain why an elevated tissue pressure in inflamed pulps may persist locally for a long time [13] without extensive damage to the pulp. If the inflammatory agents are removed, a normalization of pressure can take place and healing of the tissue occur (reversible pulpitis). However, a significant increase in interstitial fluid pressure, due to a strong and widespread inflammatory response, may seriously impede pulpal blood flow by compression of venules which contribute to pulp necrosis development. Other contributing factors to necrosis development can take place when the endothelium is exposed to bacterial endotoxins. The endothelium will respond with production of vasoconstrictors that will reduce blood flow [14] and is also shown to participate in procoagulant reactions that promote fibrin clot formation [15].

Immune cells in pulp

Resident immune cells in the pulp can respond to an inflammatory or infectious insults by innate and adaptive immune responses [16][17]. Inflammatory mediators initiating these responses can be released from carious dentin, odontoblasts, or resident pulp cells.

Odontoblasts represent the first line of detection and defense against external irritants and participate in the initiation of inflammatory and/or immune responses. They express Toll‐like receptors (TLRs), a group of transmembrane glycoproteins, that recognize various elements of microbes, viruses, and fungi [18][19]. After early activation of the odontoblasts, innate immune responses are initiated by recruitment of immune cells, production of antimicrobial peptides, and maturation of dendritic cells [18]. They secrete several products with a broad spectrum of antimicrobial and immunomodulatory activities [20][21], such as the induction of pro-inflammatory cytokine production in immune cells, chemoattraction, dendritic cell maturation and macrophage differentiation. Proteinase‐activated receptors (PARs) are receptors that undergo proteolytic activation by proteases. They participate in controlling a wide range of biological processes, such as inflammation, hemostasis, thrombosis, and hard tissue formation. PAR‐1 and ‐2 are present in human odontoblasts [22]. The expression is significantly increased in response to caries, both in the odontoblasts [22] and in pulp tissue, indicating a regulatory role in reparative dentin formation and/or in pulp inflammation.

Resolution or advancement of the initial inflammation is further regulated by a complex network of inflammatory chemokines which promote recruitment of immune cells and regulate other inflammatory responses. The dendritic cells migrate to regional lymph nodes for antigen-presentation to naïve T-cells. Activated T cells can then enhance B-cell proliferation, followed by development of antibody-producing plasma cell. Neutrophils and macrophages are professional phagocytes in innate immune responses and are recruited to the pulp in the initial phase of inflammation.

Inflammation and hypersensitivity

Hypersensitivity of dentin may also be explained by the hydrodynamic theory. In addition to sprouting of nerve fibers during inflammation (figure 5), new sodium channels, capable of activating nerves, are upregulated in the nerve fibers under inflammatory conditions [38]. An increase in the density of both nerves and sodium channels increases the sensitivity of dentine, thus resulting in hypersensitivity. Hypersensitivity also typically occurs in the cervical area where the dentin is exposed because the protective enamel/cement is worn out or etched away (figure 4). The odontoblasts and/or pulp cells respond by forming intratubular deposits or eventually tertiary dentin. This results in narrowing or closing of the dentinal tubules. Deposition of tertiary dentin leads to decreased conductivity compared to the primary and secondary dentin. This may also reduce the sensitivity, as reparative dentin is less innervated by sensory nerve fibers.

Structural changes

Aging results in cellular and extracellular changes of the dentin-pulp complex. Formation of the highly mineralized peritubular dentin causes a reduction in tubular lumen diameter, even with complete occlusion of the tubule. Age-related root tubular sclerosis starts from the apical region (figure 6A) and advances coronally [39][40], influencing root dentin permeability [41][42]. This may thus reduce bacterial penetration of dentinal tubules in elderly. Aging odontoblasts show a reduction in cell organelles, together with reduced size and polarization [43]. Pulp cell density is reduced, and the number of nerves and blood vessels is decreased [44]. The amount of collagen in the pulp increases, resulting in fibrotic changes, whereas calcifications, both diffuse and localized, are more common (figure 6B and C). Although pulp stones are considered as normal anatomical entities (figure 6D), their size may increase during aging. Diffuse mineralization, however, is a result of age changes or inflammatory conditions in the dental pulp [45].

Dimensional changes

An aged pulp characterized by “restorative scar tissues”, fibrosis and mineralization will have a reduced draining capacity, thus making it more vulnerable to circulatory failure [6]. To counteract these structural changes, increased dentin thickness may protect the pulp from external stimuli. Over time there will be a progressive linear reduction in the pulp volume, due to the continued production of dentin [46]. This process can be accelerated due to irritation from caries, restorations, or periodontal disease (figure 7). Also, cementum apposition over years may change the anatomical landmarks in the apical region (figure 6A).