Pulpal and Periapical Pathology

Dental caries results from the bacterial consumption of fermentable sugars, namely by Streptococcus mutans and Lactobacillus.

The byproduct of fermentation is acid, which dissolves dental hard tissues, resulting in a caries lesion.

Caries is a well-documented causative factor for pulpal inflammation.

Mjor and Tronstad - Reproducibly induced severe pulpal inflammation in monkeys by inserting human carious dentin into class V cavity preparations.

Reeves and Stanley - Correlated pulpal responses with depth of bacterial penetration.

• Mild chronic inflammation was evident once bacteria reached 1.1 mm from the pulp
• Severe acute inflammation was observed when bacteria reached within 0.5 mm of the pulp tissue.

Mitchell and Tarplee - Correlated these histologic findings with clinical responses when they noted histologic pulp exposures in patients with a history of spontaneous pain and radiographically detectable caries.

Cameron - Reported that coronal fractures are associated with both chewing discomfort and unexplained thermal sensitivity.

Turp and Gobetti - Reported that  sensitivity associated with a cracked tooth likely results from fluid movement within the crack causing pulpal stimulation.

Fractures also provide bacteria with a direct route into pulp tissues. In a histologic study,

Walton et al. - Visualized bacteria in fractured specimens extending from the external tooth surface to the pulp spaces. 

Robertson et al. - This ingress may explain the development of pulp necrosis and apical periodontitis in otherwise intact traumatized teeth.

Treatments aimed at eliminating caries and splinting coronal fractures have a marked effect on pulp tissues, and these effects appear to be cumulative over a lifetime.

This explains the finding that restorative treatment can cause pulpal irritation not only when treatment is initially rendered but also many years later.

Hamilton and Kramer.

• Found that dry cavity preparation injured pulp tissues more than wet cavity preparation.
• Prolonged dentin dehydration increased pulpal inflammation and caused aspiration of odontoblastic nuclei into the dental tubules.

Zach and Cohen - found that a temperature increase of 5.6°C, which is expected when preparation is performed without coolant, may cause permanent damage.

Murray et al.

• Found that a remaining dentin thickness of 0.5 mm or greater is necessary to avoid evidence of pulpal injury.
• Deeper restorative preparations decreased odontoblast numbers.
• He observed reparative dentin formation following pulp exposures and reactionary dentin formation with 0.77 mm of remaining dentin thickness.

Murray et al.

Oserved reparative dentin formation following pulp exposures and reactionary dentin formation with 0.77 mm of remaining dentin thickness.

• The percentage of crowned teeth requiring endodontic therapy is low based on literature
• reports.

• Valderhaug et al. - reported that only 8% of crowned vital teeth required root canal therapy after 10 years. After 25 years, 17% of crowned vital teeth required root canal therapy.
• Saunders and Saunders - reported that 19% of crowned teeth required endodontic therapy after cementation. If the crown is an abutment for a partial denture, a larger percentage of teeth may require endodontic intervention.
• Cheung et al. - found that 32% of partial denture abutments required endodontic therapy after cementation of the prosthesis.

The majority of published data indicate that pulpal changes caused by thermal insults are minor and pose few long-term consequences.

• Dowden et al found that low-temperature stimulation caused only minor injuries to the odontoblastic layer and microvascular system.
• Rickoff et al described similar findings with high-temperature stimuli.

These studies suggest that pulp vitality assessment with either warm or cold stimuli pose no threat to pulpal health.

Mazur and Massler, Czarnecki and Schilder, and Bender and Seltzer assert that periodontitis cannot cause pulpal disease.

As support for this idea, Seltzer et al pointed out that, while lateral canals are often exposed by periodontal disease, pulpal reactions are rarely observed.

Sinai and Soltanoff - found that pulpal lesions formed in response to periodontitis occur gradually and are more often resorptive or proliferative than inflammatory in nature.

Giovanella et al - found lower oxygen saturation rates in the pulpal tissues of teeth affected by periodontal disease than controls, though no differences in electric sensitivity testing were found.

• Landay et al - found that light excessive occlusal forces over short periods did not cause significant pulpal changes in rats.
• Glickman et al - found that high occlusion in dogs led to the influx of inflammatory cells in the pulp furcation in only 1 in 20 animals.
• Caviedes-Bucheli et al - found an increase in substance P (SP) expression in both the pulp and periodontal ligament (PDL) after an acute episode of occlusal trauma.

Rosenberg et al - suggested that occlusal reduction is effective in reducing postoperative pain in patients with vital pulps, percussion sensitivity, preoperative pain, and in the absence of an apical radiolucency

The innate immune system does not require prior pathogen sensitization and includes functions like physical barriers, phagocytes, inflammation, nonspecific proteins, and cellular responses from macrophages, polymorphonuclear leukocytes, mononuclear cells, natural killer cells, mast cells, and basophils.

The adaptive immune system requires prior antigen sensitization and includes all B- and T-cell responses.

1. Vasodilation of pulpal vasculature

2. Pulpal blood flow increases

3. Extravasation leads to increase in tissue fluid and intrapulpal pressure

4. Pulpal blood flow decreases

Cellular

• Leukocytes
• Macrophages
• Lymphocytes

Humoral

• Immunoglobulins
• Prostaglandins
• Cytokines

Hosoya and Matsushima - found that the expression of the proinflammatory cytokine IL-1β by human dental pulp cells was stimulated by lipopolysaccharide (LPS) exposure.

Nakanishi et al - found that inflamed pulp tissue contained significantly larger amounts of IgG, IgA, IgM, elastase, and PGE2 than normal pulp tissue.

Langeland - As these micro-abscesses coalesce, the pulp tissues become necrotic.

Fabricius - Necrotic pulp tissue becomes populated by bacteria, and the process of microbial succession occurs, by which initially aerobic species are replaced by anaerobes. 

Lin and Langeland - documented that bacteria

then penetrate into the circumpulpal dentinal tubules to the edge of the necrotic front. LPS, a portion of the cell wall of gram-negative bacteria, has also been associated with pulpal and periapical symptoms.

Studies by Horiba et al, Dahlen and Bergenholtz, and Schein and Schilder all document this effect.

Mejare et al - In a systematic review, concluded that insufficient evidence exists to determine whether the presence, nature, and duration of symptoms offer accurate information about the extent of pulpal inflammation.

Support the claim that clinical signs and symptoms may not correlate with the histologic picture.

• A correlation was noted between clinical diagnoses and histologic evaluations of normal, reversibly inflamed, or irreversibly inflamed pulps.
• The clinical diagnosis of normal or reversible pulpitis matched histologic diagnosis 96% of the time, and in cases of irreversible pulpitis, 84% were matched.
• These findings are encouraging as clinical tests are relied on for treatment planning and correlation of symptoms with histology indicates that practitioners can correctly guide their treatment choices.

1. Pulpal necrosis and infection of pulp tissues

2. Spread of bacteria, LPS, and viruses into the periapical tissues

3. Activation of periapical immune responses and development of apical periodontitis

Kakehashi et al - elegantly demonstrated the association between bacterial infiltration in the pulp and the development of apical periodontitis.

Korzen et al - found more severe inflammatory responses to mixed infections than to a mono infection.

Illustrate a similar relationship with LPS

Sabeti et al - evidence supports the role of viruses in periapical pathology. These pathologic entities activate both cellular and humoral immune responses, ultimately resulting in bone resorption.

Stern et al - Lymphocytes are the predominant cell population in the development of apical periodontitis.

Torabinejad and Kettering - While both T and B cells are present, the average number of T cells is typically greater than the number of B cells.

Stashenko and Yu

Helper T (TH) cells, suppressor T (TS) cells, and cytotoxic T cells.

TH cells predominate during the early, active phase of the lesion development, whereas TS cells are more numerous in chronic lesions.

Waterman et al -B cell deficiencies do not appear to alter lesion development 

Tani et al - lesion progression appears to be slowed by deficiencies in T cell populations

In addition to lymphocytes, macrophage/monocyte cells, plasma cells, polymorphonuclear leukocytes (Stern et al), natural killer cells, dendritic cells (Nilsen et al), and mast cells (Ledesma-Montes et al) have been implicated in the development of apical periodontitis.

Pulver et al - Immunoglobulins present in periapical lesions include IgG, IgA, IgE, and IgM, with IgG predominating.

PGs are metabolic byproducts of arachidonic acid formed via the cyclooxygenase pathways. They hold many functions, including gastrointestinal homeostasis, promotion of inflammation, vasodilation, chemotaxis, pain, vascular permeability, and bone resorption.

McNicholas et al - Symptomatic lesions have a significantly higher concentration ofPG activity than chronic lesions or uninflamed tissues.

Stashenko et al - Cytokines, including IL-1β and IL-1α, are produced by inflammatory cells in apical periodontitis.

Sousa et al, Martinho et al - Endodontic pathogens activate toll-like receptor 4 on macrophages leading to the expression of IL-1β, tumor necrosis factor α (TNFα), IL-6, and IL-10.

Sabeti et al and Hernadi et al recently discovered that viral infections promote cytokine production in periapical lesions.

Stashenko - IL-1β is the most active bone resorptive cytokine, reported to have approximately 15 times greater potency than IL-1α.

Morsani et al - Genetic differences in IL-1β production have been associated with persistent apical periodontitis.

Kobayashi et al - Cytokines, including IL-1, TNFα, and leukotriene, promote the fusion of osteoclast precursor cells and cause consequent bone resorption

Gomes et al found - that apical periodontitis is  associated with increased systemic levels of C reactive protein, IL-6, IL-1, IL-2, IgA, IgG, and IgM in humans.

Alternatively, systemic medications may mitigate the humoral response.

• Lin et al found that administration of simvastatin decreased the expression of pro inflammatory cytokines and attenuated bone resorption in rats.
• Liu et al - found that metformin had similar results.

Cytokines produced during inflammatory responses stimulate the production of a molecule called receptor activator of nuclear factor k-B ligand (RANKL) by immune competent cells, which ultimately results in the destruction of bone by osteoclasts.

Osteoblasts, rather than osteoclasts, possess the receptors for resorptive hormones and cytokines.

In the functional absence of osteoblasts, osteoclasts cannot respond to resorptive mediators. Bacteria and LPS may also directly activate cells, including periapical T cells, to produce RANKL, thus stimulating osteoclasts to resorb bone.

Matsumiya and Kitamura, Tronstad et al, Sundqvist and Reuterving, and Iwu et al located bacteria in periapical tissues.

Wayman et al - found more bacteria in lesions that communicated with the oral cavity.

In addition to histologic data, newer DNA probe techniques have also been used to demonstrate bacteria in apical lesions. Saber et al used this technique to locate bacteria in symptomatic lesions.

Shindell as well as Walton and Ardjmand were unable to detect viable bacteria within periapical tissues.

Siqueira and Lopes noted that bacteria were restricted to the root canal space in teeth without previous root canal therapy.

Despite the controversy regarding localization of live bacteria, however, a relationship between bacteria and apical periodontitis is undeniable.

Studies by Linenberg et al, Stockdale and Chandler, Wais, Baumann and Rossman, and Lalonde all demonstrated the inability to correlate histologic diagnoses with radiographic findings.

These findings, taken together with the small chance of locating other pathologic entities, underscore the importance of histologic examination of periapical specimens.

Peters and Lau - suggest that histologic evaluation of a periapical lesion is appropriate any time recoverable tissue is present.

Ricucci et al - found no correlation between the presence of a radiopaque lamina and the histologic diagnosis of a cyst.

Granuloma

• May contain epithelial cells, though no epithelial
• lining is present
• Contain immune cells
• Humoral immunity, IgG most common

Cysts

• Epithelial-lined cavity
• Contain immune cells
• Humoral immunity, IgG and IgA

Periapical granulomas are composed of granulation tissue and chronic inflammation rather than granulomatous inflammation as the nomenclature suggests.

Nair et al - The organization of epithelial cells in cystic lesions, rather than the simple presence of epithelial cells, is what differentiates periapical cysts from periapical granulomas.

• Ten Cate - Nutritional deficiency theory
• Nair - Abscess theory
• Torabinejad - Immunologic theory

Ten Cate proposed the nutritional deficiency theory, asserting that cells in the center of the epithelial cavity lose their nutritional source and necrose.

The abscess theory suggests that proliferating epithelial cells line an existent abscess cavity as a result of the inherent nature of epithelial cells to cover exposed connective tissue surfaces.

Torabinejad’s immunologic theory proposes that the inflammatory mediators present in periapical responses stimulate epithelial cells to proliferate.

True cysts represent epithelial-lined lesions that do not attach to the root canal system, whereas bay cysts communicate with the periapex.

Nair et al - found that true cysts were more common than bay cysts, also known as pocket cysts.

Bhaskar theorized that cysts can heal after nonsurgical root canal therapy, as the frequency of cysts diagnosed via biopsy is larger than failure rates examined in prognostic literature.

Sirotheau Correa Pontes et al - 66% of non-endodontic lesions found at the periapex were benign, 29% were malignant, and 5% represented Stafne bone cavities.

Orthokeratinized odontogenic cysts, central giant cell granulomas, periapical giant cell granulomas, lymphomas, fungal infections, actinomycosis, central ossifying fibromas, Langerhans cell histiocytosis, osteoblastomas, central ossifying fibromas, osteosarcoma, plasma cell tumors, and metastatic lesions among others.

The existence of these entities again underscores the necessity for pathologic evaluation of any tissue removed from the periapex.

Nair et al - found that periapical biopsy specimens contained granulomas 50% of the time, abscesses 35% of the time, and cysts 15% of the time. Of the cysts, 61% represented true cysts, whereas 39% represented pocket cysts. 

Koivisto et al - In another study that diagnosed 9,723 biopsy specimens, diagnosed granulomas in 40% of cases and cysts in 33% of cases.

Yu et al - found only a 5.8% incidence of flare-up after initiation of root canal therapy on teeth with periapical lesions.

• Walton and Fouad - associated flare-ups
• with female sex, complaints of preoperative pain and swelling, and pulpal necrosis.

Torabinejad - associated flare-ups with retreatment therapy and a history of allergies.

Walton and Fouad - they cannot be prevented with antibiotic administration

Seltzer and Naidorf - Analgesics and antibiotics may be used to control a flare-up once initiated.

de Chevigny - Though uncomfortable, flare-ups have not been associated with treatment failures.