The dental pulp is a dynamic tissue that responds to external stimuli in many ways. However, there are certain unique features about the dental pulp response that distinguish it from other connective tissues in the body. The pulp’s exposure to dental caries, a prevalent chronic infectious disease, its encasement in an unyielding environment after complete tooth maturation, and the scarcity of collateral circulation render it susceptible to injury and complicate its regeneration. Moreover, the pulp is endowed with a rich neurovascular supply that regulates the effects of inflammation that may ultimately lead to rapid degeneration and necrosis. The treatment of dental caries and other tooth abnormalities involves removal of the enamel and dentin, the hardest tissues in the body, thus adding to the irritation of the pulp. This chapter discusses the response of the pulp to all of these variables and presents advances in our understanding of dental procedures and their effects on the pulp.
Pulpal Reaction to Caries
Dental caries is a localized, destructive, and progressive infection of dentin, which, if left unchecked, can result in pulpal necrosis and potential tooth loss. Both bacterial by-products and products from the dissolution of the organic and inorganic constituents of dentin mediate the effects of dental caries on the pulp. Three basic reactions tend to protect the pulp against caries: (1) a decrease in dentin permeability, (2) tertiary dentin formation, and (3) inflammatory and immune reactions. These responses occur concomitantly, and their robustness is highly dependent on the aggressive nature of the advancing lesion as well as host responses such as the age of the patient (see also Chapter 26 ).
In the advancing infection front of the carious lesion, multiple intrinsic and extrinsic factors are released that stimulate nearby pulpal tissue. Bacterial proteolytic enzymes, toxins, and metabolic by-products have been thought to initiate pulpal reactions, yet the buffering capacity of dentin and dentinal fluid likely attenuate these deleterious effects. This protective function is significantly reduced when the remaining dentin thickness is minimal. When relatively unhindered access to pulpal tissue is present, both bacterial metabolites and their cell wall components induce inflammation. In initial-to-moderate lesions, current evidence suggests that acidic by-products of the carious process act indirectly by degrading the dentin matrix and thereby liberating bioactive molecules previously sequestered during dentinogenesis. Once liberated, these molecules again assume their role in dentin formation, this time stimulatory for tertiary dentinogenesis. This theory is supported by the findings that demineralized dentin matrix implanted at the site of pulpal exposure can induce dentinogenesis. Furthermore, placement of purified dentin matrix proteins on exposed dentin or exposed pulp stimulates tertiary dentin formation, indicating that these molecules can act directly or across intact dentin. More information on growth factors embedded in dentin is reviewed in the chapter on regenerative endodontics (see Chapter 10 ).
Evidence offers several candidate molecules that stimulate reparative dentinogenesis. Heparin-binding growth factor, transforming growth factor (TGF)-β1, TGF-β3, insulin-like growth factors I and II, platelet-derived growth factor, bone morphogenetic protein-2 (BMP-2) and angiogenic growth factors have been shown to be embedded in dentin and stimulatory for dentinogenesis in vitro. The TGF-β superfamily in particular seems to be important in the signaling process for odontoblast differentiation from mesenchymal stem or progenitor cells as well as primary and tertiary dentinogenesis. As the predominant isoform, TGF-β1 is equally distributed in the soluble and insoluble fractions of dentin matrix. During the carious dissolution of dentin, it is believed that the soluble pool of TGF-β1 can diffuse across intact dentin while the insoluble pool is immobilized on insoluble dentin matrix and serves to stimulate odontoblasts much like membrane-bound TGF-βs during odontogenesis.
Despite the research interest in tertiary dentinogenesis, it is neither the first nor necessarily the most effective pulpally mediated defense against invading pathogens. A combination of an increased deposition of intratubular dentin and the direct deposition of mineral crystals into the narrowed dentin tubules to decrease dentin permeability is the first defense to caries and is called dentin sclerosis . It occurs by a combination of increased deposition of intratubular dentin and tubule occlusion by precipitated crystals. This results in an effective decrease in dentin permeability underneath the advancing carious lesion. In vitro studies with cultured tooth slices implicate TGF-β1 as a central player in the increased deposition of intratubular dentin. The deposition of whitlockite crystals in the tubular lumen most likely results from a similar stimulation of vital associated odontoblasts, possibly in combination with precipitation of mineral released during the demineralization process ( Fig. 13-1 ).
The formation of tertiary dentin occurs over a longer period than does that of sclerotic dentin, and its resultant character is highly dependent on the stimulus. Mild stimuli activate resident quiescent odontoblasts whereupon they elaborate the organic matrix of dentin. This type of tertiary dentin is referred to as reactionary dentin and can be observed when initial dentin demineralization occurs beneath the noncavitated enamel lesion. Mediators present during the carious process induce a focal upregulation of matrix production by resident odontoblasts. The resultant dentin is similar in morphology to physiologic dentin and may only be apparent due to a change in the direction of the new dentinal tubules ( Fig. 13-2 ). In contrast, in aggressive lesions the carious process may prove cytocidal to subjacent odontoblasts and require repopulation of the disrupted odontoblast layer with differentiating progenitors. The organization and composition of the resultant matrix are a direct reflection of the differentiation state of the secretory cells. This accounts for the heterogeneity of reparative dentin, where the morphology can range from organized tubular dentin to more disorganized irregular fibrodentin . Fibrodentin, due to its irregular configuration and tissue inclusions, is more permeable than physiologic dentin ( Fig. 13-3 ).
Although dentin can provide a physical barrier against noxious stimuli, the pulpal immune response provides humoral and cellular challenges to invading pathogens. In the progressing carious lesion, the host immune response increases in intensity as the infection advances. It has been shown that titers of T-helper cells, B-lineage cells, neutrophils, and macrophages are directly proportional to lesion depth in human teeth. The disintegration of large amounts of dentin, however, is not necessary to elicit a pulpal immune response. This is supported by the observation that a pulpal inflammatory response can be seen beneath noncavitated lesions and noncoalesced pits and fissures.
The early inflammatory response to caries is characterized by the focal accumulation of chronic inflammatory cells ( Fig. 13-4 ). This is mediated initially by odontoblasts and later by dendritic cells. As the most peripheral cell in the pulp, the odontoblast is positioned to encounter foreign antigens first and initiate the innate immune response. Pathogen detection in general is accomplished via specific receptors called pattern recognition receptors (PRRs). These receptors recognize pathogen associated molecular patterns (PAMPs) on invading organisms and initiate a host defense through the activation of the NF-κB pathway. One class of the PAMP recognition molecules is the Toll-like receptor family (TLRs). Odontoblasts have been shown to increase expression of certain TLRs in response to bacterial products. Under experimental conditions, odontoblasts expression of TLR3, 5, and 9 increased in response to lipoteichoic acid, whereas lipopolysaccharide increased TLR2 and 4 expression. It was also shown that TGFβ-1 inhibits the expression of TLR2 and 4 by odontoblasts in response to gram-positive and gram-negative bacteria. Once the odontoblast TLR is stimulated by a pathogen, proinflammatory cytokines, chemokines, and antimicrobial peptides are elaborated by the odontoblast, resulting in recruitment and stimulation of immune effector cells as well as direct bacterial killing.
Many cells produce chemokines at low levels constitutively. Unstimulated odontoblasts express genes coding for CCl2, CXCL12, and CXCL14, three genes known to code for factors chemotactic for immature dendritic cells. They also produce CCL26, a natural antagonist for CCR1, CCR2, and CCR5 that are chemokines normally produced by monocytes and dendritic cells. Stimulation with bacterial cell wall constituents has been shown to upregulate the expression of multiple chemokine genes including CXCL12, CCL2, CXCL9, CX3CL1, CCL8, CXCL10, CCL16, CCL5, CXCL2, CCL4, CXCL11, and CCL3, and nine chemokine receptor genes including CXCR4, CCR1, CCR5, CX3CR1, CCR10, and CXCR3, suggesting that odontoblasts sense pathogens and express factors that recruit immune effector cells ( Fig. 13-5 ). These data suggest a scenario whereby stimulated odontoblasts express high levels of chemokines such as IL-8 (CXCL8) that act in concert with the release of formerly sequestered growth factors from carious dentin that induce a focal increase in dendritic cell numbers with the additional release of chemotactic mediators. The subsequent influx of immune effector cells is composed of lymphocytes, macrophages, and plasma cells. This cellular infiltrate is accompanied by localized capillary sprouting in response to angiogenic factors as well as co-aggregation of nerve fibers and human leukocyte antigen-DR (HLA-DR)-positive dendritic cells.
As the carious lesion progresses, the density of the chronic inflammatory infiltrate as well as that of dendritic cells in the odontoblast region increases. Pulpal dendritic cells are responsible for antigen presentation and stimulation of T lymphocytes. In the uninflamed pulp they are scattered throughout the pulp. With caries progression they aggregate initially in the pulp and subodontoblastic regions, then extend into the odontoblast layer, and eventually migrate into the entrance to tubules beside the odontoblast process ( Fig. 13-6 ). Two distinct populations of dendritic cells have been identified in the dental pulp. CD11c+ is found in the pulp/dentin border and subjacent to pits and fissures. F4/80+ dendritic cells are concentrated in the perivascular spaces in the subodontoblastic zone and inner pulp. CD11c+ dendritic cells express Toll-like receptors 2 and 4 and are CD205 positive. F4/80+ dendritic cells have migratory ability. As they migrate from the central pulp they increase in size and become CD86 positive. The close spatial relationship between odontoblasts and dendritic cells under the carious lesion has led to speculation that dendritic cells may play a role in odontoblast differentiation or secretory activity in the immune defense and in dentinogenesis. Recent studies have demonstrated that pulp dendritic cell can migrate to regional lymph nodes, for antigen presentation. In vitro studies have suggested that the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) and osteopontin by dendritic cells and macrophages represents a mechanism whereby they contribute to odontoblast differentiation. Pulpal Schwann cells have also been shown to produce molecules in response to caries, which indicates the acquisition of the ability for antigen presentation.
Evidence suggests that odontoblasts also play a role in the humoral immune response to caries. IgG, IgM, and IgA have been localized in the cytoplasm and cell processes of odontoblasts in human carious dentin, suggesting that these cells actively transport antibodies to the infection front. In the incipient lesion, antibodies accumulate in the odontoblast layer and with lesion progression can be seen in the dentinal tubules. Eventually this leads to a focal concentration of antibodies beneath the advancing lesion.
In the most advanced phase of carious destruction, the humoral immune response is accompanied by immunopathologic destruction of pulpal tissue. In animal studies where monkeys were hyperimmunized to bovine serum albumin (BSA), there was an observed increase in pulpal tissue destruction subsequent to antigenic challenge across freshly cut dentin. The odontoblasts also appear to be involved in the production of innate antimicrobial molecules such as human beta defensing-2 (HBD2). Therefore, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha as well as bacterial lipopolysaccharide (LPS) were responsible for significant increases in HBD2 in response to caries. In summary, it appears the odontoblasts play a central role in orchestrating local and chemotactic inflammatory responses to dental caries ( Fig. 13-7 ).
Pulpal exposure in primary and immature permanent teeth can lead to a proliferative response or hyperplastic pulpitis . Exuberant inflammatory tissue proliferates through the exposure and forms a “pulp polyp” ( Fig. 13-8 ). It is presumed that a rich blood supply allows this proliferative response. Conventional root canal therapy or progressive vital pulp therapy is indicated.
Neurogenic mediators are involved in the pulpal response to irritants and, like immune components, they can mediate pathology as well as the healing response (see also Chapter 12 ). External stimulation of dentin causes the release of pro-inflammatory neuropeptides from pulpal afferent nerves. Substance P (SP), calcitonin gene–related peptide (CGRP), neurokinin A (NKA), neurokinin Y, and vasoactive intestinal peptide are released and effect vascular events such as vasodilation and increased vascular permeability. This results in a net increase in tissue pressure that can progress to necrosis in extreme and persistent circumstances. Stimulation of sympathetic nerves in response to the local release of mediators such as norepinephrine, neuropeptide Y, and adenosine triphosphate (ATP) has been shown to alter pulpal blood flow. Receptor field studies as well as anatomic studies have shown sprouting of afferent fibers in response to inflammation.
Neuropeptides can act to modulate the pulpal immune response. It has been demonstrated that SP acts as a chemotactic and stimulatory agent for macrophages and T lymphocytes. The result of this stimulation is increased production of arachidonic acid metabolites, stimulation of lymphocytic mitosis, and production of cytokines. CGRP demonstrates immunosuppressive activity, which is evidenced by a diminution of class II antigen presentation and lymphocyte proliferation.
SP and CGRP are mitogenic for pulpal and odontoblast-like cells; thereby they initiate and propagate the pulpal healing response. CGRP has been shown to stimulate the production of bone morphogenic protein by human pulpal cells. The result of this stimulation has been postulated to induce tertiary dentinogenesis. Substance P appears to increase in the dental pulp and periodontal ligament as a result of acutely induced occlusal trauma, which may be related to the pain associated with concussion traumatic injury.
It has been shown that there may be gender differences in CGRP release in the dental pulp. In one study, serotonin (a peripheral pronociceptive mediator) induced a significant increase in capsaicin-evoked CGRP release in dental pulps obtained from female but not male patients. This interplay of inflammatory mediators may explain some of the gender differences in clinical presentation with dental pain.
Correlation Between Clinical Symptoms and Actual Pulpal Inflammation
From a clinical perspective, it would be most helpful to the clinician to be able to diagnose pulpal conditions from a profile of symptoms with which a patient presents. If symptoms are not conclusive, a number of objective tests should aid the clinician in reaching a definitive diagnosis of the pulpal pathologic status. In actuality, combinations of subjective and objective findings are frequently insufficient in reaching definitive diagnosis of the status of the dental pulp. This is particularly true in cases of vital inflamed pulp, where it is difficult for the practitioner to determine clinically whether the inflammation is reversible or irreversible.
Many practitioners rely on painful symptoms to determine the status of the pulp. Several studies have examined this question in some detail. A number of classic studies were performed in which the subjective and objective clinical findings related to carious teeth were recorded prior to extracting the teeth and examining them histologically. The underlying hypothesis in these studies was that the more severe the clinical symptoms, the more intense pulpal inflammation and destruction was evident histologically. These studies showed that in the vital pulp, clinical symptoms generally did not correlate with gross histologic findings. Furthermore, carious pulp exposure was associated with severe inflammatory response or liquefactive necrosis, regardless of symptoms ( Fig. 13-9 ). These histologic changes ranged in extent from being present only at the site of the exposure to deep into the root canals. In a few studies prolonged or spontaneous severe symptoms were associated with chronic partial, total pulpitis, or pulp necrosis. However, in these as well as other studies it was common to find cases with evidence of severe inflammatory responses including partial necrosis histologically, but with little or no clinical symptoms—the so-called painless pulpitis. Moreover, the density of nerve fibers and the vascularity in inflamed pulp do not correlate with clinical symptoms in primary and permanent teeth. It has been reported that the incidence of painless pulpitis that leads to pulp necrosis and asymptomatic apical periodontitis is about 40% to 60% of all pulpitis cases.
Objective clinical findings are essential for determining the vitality of the pulp and whether the inflammation has extended into the periapical tissues (see also Chapter 1 ). Lack of response to electric pulp testing generally indicates that the pulp has become necrotic. Thermal pulp testing is valuable for reproducing a symptom of thermal sensitivity and allowing the practitioner to assess the reaction of the patient to a stimulus and the duration of the response. However, pulp testing cannot determine the degree of pulpal inflammation. These studies show that irreversible pulpal inflammation can be diagnosed with some certainty only in cases where, in addition to being responsive to pulp testing, the pulp develops severe spontaneous symptoms. Pulp necrosis could be predictably diagnosed by a consistent negative response to pulp tests, preferably to both cold and electrical tests to avoid false responses. Pulp necrosis could be verified by a test cavity or lack of hemorrhagic pulp tissue upon access preparation. It should be noted, however, that the latter sign should be assessed cautiously. Occasionally, the pulp space is very small, such as in older individuals with calcified canals, and hemorrhage upon access to the pulp may not be clinically appreciable. Conversely, cases with pulp necrosis and acute periapical infections may have hemorrhagic purulent drainage through the large pulp space upon access preparation, particularly after initial instrumentation.
The lack of correlation between the histologic status of the pulp and clinical symptoms may be explained by advances in the science of pulp biology. Studies have shown that numerous molecular mediators may act in synchrony to initiate, promote or modulate the inflammatory response in the dental pulp. The nature and quantity of these inflammatory mediators cannot be determined from histologic analysis, without the use of specialized staining techniques. Many of these molecular mediators tend to reduce the pain threshold, either directly by acting on peripheral nerve cells or by promoting the inflammatory process. Thus, a number of these mediators were shown to be elevated in human pulp diagnosed with painful pulpitis. These mediators include prostaglandins, the vasoactive amine bradykinin, tumor necrosis factor alpha, neuropeptides such as substance P, CGRP and neurokinin A, and catecholamines. In fact, it was even shown that when patients have painful pulpitis, the crevicular fluid related to the affected teeth has significantly increased neuropeptides compared to the levels in contralateral teeth. In another study, trained volunteers stimulated an incisor with a constant current three fold the threshold value for 90 seconds. This resulted in a significant increase in crevicular matrix metalloproteinase 8 (MMP-8), one of the collagenases involved in tissue destruction.
It has also been determined that peripheral opioid receptors are present in the dental pulp, and these could play a role in why many cases with irreversible pulpitis are asymptomatic. As noted before, carious teeth are frequently not associated with significant symptoms. However, they still have a significant amount of inflammation. The pulp in teeth with mild to moderate caries has increased neuropeptide Y, and its Y1 receptor, compared to that in normal teeth. Neuropeptide Y is a neurotransmitter for the sympathetic nervous system and is thought to act as a modulator of neurogenic inflammation. Likewise, the levels of vasoactive intestinal peptide (VIP), although not its receptor VPAC1, seemed to increase in the pulp of moderately carious teeth.
With the advances in molecular biology, efficient detection of hundreds of molecular mediators simultaneously by their gene expression has become a reality. Current research seeks to examine which genes are specifically expressed or upregulated in the pulp, in response to the carious lesion. In this regard, preliminary studies have shown that various cytokines and other inflammatory mediators are upregulated underneath a carious lesion in a manner that correlates with the depth of caries. Several researchers have used gene microarrays to obtain an accurate mapping of candidate genes that show elevated expression in inflamed pulp and the odontoblastic cell layer. In addition, research has revealed the differential expression of microRNAs (miRNAs) in the healthy and diseased dental pulp. MiRNAs are noncoding RNA molecules that regulate gene expression in complex inflammatory responses and may eventually assist in clinical predictions of pulpal status. Therefore, more accurate chair-side diagnostic methods are potentially feasible to develop, especially a method that involves sampling from crevicular fluid, dentinal fluid, or the pulp directly. For this reason, more research is needed to determine the key mediators that would predict survival or degeneration of the dental pulp in difficult diagnostic cases.
Dentin Hypersensitivity and Its Management
Dentin hypersensitivity is a special situation in which a significant, chronic, pulpal pain arises, which does not seem to be associated with irreversible pulpal pathosis in the majority of cases. Dentin hypersensitivity is characterized by brief sharp pain arising from exposed dentin in response to stimuli, typically thermal, evaporative, tactile, osmotic, or chemical, that cannot be ascribed to any other form of dental defect or pathosis. Facial root surfaces in canines, premolars, and molars are particularly affected, especially in areas of periodontal attachment loss. Dentin hypersensitivity may be related to excessive abrasion during tooth brushing, periodontal disease, or erosion from dietary or gastric acids, and it may increase following scaling and root planing. The dentin is hypersensitive, most likely due to the lack of protection by cementum, loss of smear layer by acidic dietary fluids, and the hydrodynamic movement of fluid in dentinal tubules. The degree of inflammation in the pulp in cases of dentin hypersensitivity is not well characterized, because the condition is usually not severe enough to warrant tooth extraction or endodontic therapy. However, patent dentinal tubules are present in areas of hypersensitivity ( Fig. 13-10 ) and may result in increased irritation and localized reversible inflammation of the pulp at the sites involved.
The application of neural modulating agents such as potassium nitrate, or tubule blocking agents such as strontium chloride, oxalates or dentin bonding agents ( Fig. 13-11 ), usually alleviates the condition, at least temporarily. However, the placement of passive molecules or crystals may provide only temporary relief, thus there has been the need to provide biocompatible materials that bond to the root surface in order to provide a more lasting solution. One such material was a calcium sodium phosphosilicate bioactive glass, which was developed into a commercial product (SootheRx, NovaMin Technology Inc., Alachua, FL). Another product uses a combination of a calcium oxalate and an acid-etched bonding material to seal the dentinal tubules (BisBlock, Bisco Inc., Schaumberg, IL). A concern has been raised that the acidic pH during etching may cause dissolution of the oxalate crystals, thus interfering with the effectiveness of the material. However, one study found that BisBlock and two other products—Seal&Protect (Dentsply Professional, York, Pennsylvania) and Vivasens (Ivoclar Vivadent AG, Schaan, Liechtenstein)—were effective compared to placebo several weeks after treatment. In the long term, the development of smear layer, such as from tooth brushing, dentin sclerosis, reactionary dentin, and the blockage of tubules with large endogenous macro molecules, is all thought to reduce the problem (see animation from the online edition of this chapter). A practice-based, randomized clinical trial compared the effectiveness of non-desensitizing toothpaste (Colgate Cavity Protection Regular, Colgate-Palmolive, New York, New York), desensitizing toothpaste (Colgate Sensitive Fresh Stripe, Colgate-Palmolive), and a professionally applied desensitizing agent (Seal & Protect). The findings showed a significant reduction of dentin hypersensitivity in the desensitizing therapies compared to the non-desensitizing group that was a much more significant reduction in the professionally applied desensitizing agent over a 6-month period.
Pulpal Reactions to Local Anesthetics
An intact pulpal blood flow is critical for maintaining the health of the dental pulp. Because the dental pulp is enclosed in a rigid chamber and is supplied by few arterioles through the apical foramina, it cannot benefit from collateral circulation or volumetric changes that compensate for changes in blood flow in other soft tissues. Furthermore, reduction in blood flow has the compounding effect of reducing the clearance of large molecular weight toxins or waste products, thus causing irreversible pulpal pathosis. Vasoconstrictors are added to local anesthetics to enhance the duration of anesthesia. However, vasoconstrictors in local anesthetics could negatively impact the health of the pulp if they reduce blood flow, particularly if the pulp is inflamed preoperatively. Earlier studies have documented that vasoconstrictors in local anesthetics do reduce pulpal blood flow in experimental animals when administered by infiltration and nerve block ( Fig. 13-12 ), and that this effect was more severe with periodontal ligament injections ( Fig. 13-13 ). More recently, clinical trials were conducted in which subjects were given infiltration of different local anesthetics with or without epinephrine at a concentration of 1 : 100,000 and the pulpal blood flow was measured by laser Doppler flowmetry. In groups that received the epinephrine, there were consistently significant reductions in pulpal blood flow, even if the infiltration was palatal to maxillary premolars. Interestingly, in one study the reduction in pulpal blood flow with epinephrine infiltration was more than the reduction in gingival blood flow and did not return to baseline values after 1 hour of injection. Similar reductions in pulpal blood flow were reported when inferior alveolar nerve block injections of lidocaine and 1 : 100,000 or 1 : 80,000 epinephrine were administered. It is important to note a limitation of studies using laser Doppler flowmetry, which is that a large proportion of the signal measured may be from sources other than the dental pulp. Thus, the monitoring of minor changes in pulpal blood flow must be interpreted with caution, particularly if the rubber dam or a similar barrier was not used. Human studies on the effects of periodontal ligament or intraosseous injections on pulpal blood flow are not available, but from animal studies it is probable that these supplemental anesthetic techniques cause a more severe reduction or even transient cessation of pulpal blood flow. It was also shown that intraosseous injection of Depo-Medrol™ (a corticosteroid) in patients with symptomatic irreversible pulpitis causes a significant reduction of prostaglandin E2 in the pulp 1 day after administration, indicating that this route of injection results in significant permeation into the pulpal tissues. Taken together, these findings suggest that local anesthesia with vasoconstrictors may compromise the inflamed pulp’s ability to recover from inflammation, particularly if it is severely inflamed, or if the tooth is subjected to extensive restorative procedures, and if the anesthetic is delivered via a periodontal ligament or an intraosseous route. However, it is important to realize that this hypothesis should be supported or refuted by prospective randomized clinical trials.
Intrapulpal anesthesia is often used as a last resort, when pulpal anesthesia is insufficient during root canal therapy. The effect of intrapulpal anesthesia on the pulp in these cases is not considered, as the pulp will be removed. However, occasionally a pulpotomy is performed to maintain pulpal vitality, such as in children where the tooth has an immature apex. One study has shown that intrapulpal anesthesia can be used in these cases, with no clinical differences on follow-up of over 24 weeks between the groups that did or did not receive intrapulpal anesthesia, and when given, in the groups where the anesthetic contained or did not contain epinephrine.
Pulpal Reactions to Restorative Procedures
A large body of literature exists on the effects of restorative procedures on the dental pulp. This topic, understandably, has been important for practicing dentists for many years. Restorative procedures are performed primarily to treat an infectious disease, dental caries, which itself causes significant irritation of the pulp. They may also be performed to help restore missing teeth; correct developmental anomalies; address fractures, cracks, or failures of previous restorations; or a myriad of other abnormalities. One key requirement of a successful restorative procedure is to cause minimal additional irritation of the pulp so as not to interfere with normal pulpal healing. When pulp vitality is to be maintained during a restorative procedure, then a provisional diagnosis of reversible pulpitis rather than irreversible pulpitis must preexist. Therefore, it would be most desirable to perform a minimally traumatic restorative procedure, which would not potentially convert the diagnosis to irreversible pulpitis. As discussed previously, irreversible pulpitis may present clinically with severe spontaneous postoperative pain, but it may also be asymptomatic, leading to the asymptomatic demise of the pulp. The additive effects of restorative procedures are particularly critical in borderline cases, such as those of moderately symptomatic teeth with deep caries but no pulp exposure. There are still many factors whose influence on the response of the dental pulp to the cumulative effects of caries, microleakage, restorative procedures, and materials is not well understood. It is generally accepted that the effects of pulpal insults, be they from caries, restorative procedures, or trauma, are cumulative—that is, with each succeeding irritation, the pulp has a diminished capacity to remain vital. As a part of informed consent, the clinician is often faced with the task of outlining possible risks of restorative treatment. One study from a hospital in Hong Kong addressed the fate of pulps beneath single-unit metal-ceramic (MC) crowns or MC bridge abutments. Patients who had received either treatment were invited to attend a recall appointment that involved both clinical and radiographic examinations. Researchers examined 122 teeth with preoperatively vital pulps treated with single-unit MC crowns and 77 treated as bridge abutments. The mean observation period was 14 years for the former and 15.6 years for the latter. Pulpal necrosis had occurred in 15.6% of the teeth treated with single-unit crowns, whereas 32.5% of the pulps in the bridge retainer groups had become necrotic. There was a significantly higher percentage of pulpal necrosis in anterior teeth that served as bridge abutments (54.5% of anterior abutment teeth examined). In general, however, the available evidence indicates that the effects of dental procedures on the pulp depend on the following factors.
The Degree of Inflammation of the Pulp Preoperatively
As stated previously, the dental pulp is compromised in its ability to respond to external irritants because it is enclosed in a noncompliant environment and because it lacks collateral circulation. Thus, the more severe the pulp is inflamed, the less will be its ability to respond to further irritation, such as in the form of restorative procedures.
Most research studies designed to evaluate the effects of restorative procedures (or materials) on the pulp are conducted on human or experimental animal teeth with normal pulp. Furthermore, many of the animal research projects have been performed on anesthetized animals without the use of local anesthesia, which as stated previously, reduces pulpal blood flow. Therefore, the results of these studies may not reveal the true effects of these procedures when the carious lesion already causes inflammation of the pulp, and pulpal blood flow is reduced by local anesthetic with vasoconstrictors. A study that evaluated the response of the pulp to capping procedures as a function of duration of exposure showed that the pulp responds favorably to exposures for up to 24 hours after exposure, but not as favorably after longer periods of exposure to the oral environment. It may be that the longer exposure periods lead to the formation of a bacterial biofilm, which is difficult for the pulpal immune responses to eliminate, or the extension of the infection so deep into the pulp as to preclude healing. This is relevant in cases of aseptic mechanical exposures or teeth where the pulp is exposed by traumatic injuries for a brief duration. In these cases, the pulp usually responds favorably to vital pulp therapy procedures. Models of standardized pulpal inflammation with chronic caries are not commonly used in determining the effects of dental procedures. Older clinical studies show an unfavorable long-term outcome of capping cases with carious pulp exposures ; however, newer studies in which mineral trioxide aggregate (MTA) was used show more favorable results in these cases.
In the absence of severe spontaneous symptoms or pulp exposure, as indicated previously, the clinician currently cannot determine accurately the degree of preoperative pulpal inflammation. Thus, every effort should be made to minimize added irritation during restorative procedures, as it is possible that excessive irritation could convert the inflammatory status of the pulp from a reversible to an irreversible condition. In addition, the patient should always be advised of the possibility of pulpal degeneration and the importance of follow-up.
The Amount of Physical Irritation Caused by the Procedure
Physical irritation during restorative procedures such as from heat, desiccation, or vibration may adversely affect the dental pulp.
Restorative procedures such as cavity or crown preparation, or curing of resins during direct fabrication of provisional restorations, may cause significant increases in pulpal temperatures. It has been shown using primate models that an intrapulpal temperature rise of 10° C causes irreversible pulp pathosis in 15%, and a 20° C rise caused pulp abscess formation in 60% of teeth evaluated. A number of other older studies documented burns or severe inflammation in the pulp when cavity or crown preparations were performed without coolants ( Figs. 13-14 to 13-16 ). However, a more recent study, in which gradual controlled heat application over a large area of the intact occlusal surface of human unanesthetized teeth was employed, failed to corroborate these earlier findings. In this study, an increase of intrapulpal temperature of about 11°C followed by a 2- to 3-month evaluation did not show any clinical or histologic changes in the pulp of any of the teeth evaluated. Heat increase in rat pulp tissue to 42° C in vitro raised heat shock protein-70, which is known to be tissue protective, and caused changes in alkaline phosphatase and gap junction proteins that were reversed to normalcy a few hours later. By contrast in another study, heat applied in deep cavity preparations, prepared atraumatically in human teeth, caused histologic changes that were dependent on the proximity of the heat source to the pulp. It was common in that study to see a loss of odontoblasts or their aspiration into the dentinal tubules. In cases where the cavity floor was less than 0.5 mm from the pulp, areas of coagulation necrosis could be seen, although the patients remained asymptomatic for the 1-month duration of the study. The measurement of heat in the tooth being prepared, in areas other than the site of tooth preparation, occasionally shows reduction in temperature, presumably because of the poor conductive properties of dentin and the cooling effect of compressed air of the high-speed hand piece. Furthermore, cavity and crown preparations include a number of other irritating stimuli such as desiccation, severance of odontoblastic processes, vibration, and smearing of bacterial irritants onto the surface of dentin. Therefore, taken together, these findings suggest that the transient increase in temperature to levels relevant to modern dental procedures on its own may not be the culprit in inducing pulpal changes. Rather, the synergistic application of excessive heat with other irritation factors and its proximity to the pulp may induce pathologic changes.
Desiccation during cavity and crown preparation has long been known to cause aspiration of odontoblastic nuclei into dentinal tubules and pulpal inflammation. One study showed that as little as 30 seconds of continuous air drying of class V cavities in human molars with uninflamed pulp caused significant displacement of odontoblastic nuclei, pulp inflammation, and even areas of necrosis related to the areas that were dried. However, another study showed that the effects of desiccation are transient in that within 7 to 30 days there is autolysis of the aspirated cells and formation of reactionary dentin. The pulp in cases with aspirated odontoblasts, following desiccation for 1 minute, was not sensitive to clinical scraping with an explorer. The sensitivity was restored with rehydration of the cavities and was increased in other cases where pulp inflammation was induced by microbial contamination. In this study, despite the lack of sensitivity in desiccated cavities, neural elements were seen histologically to be pushed into the tubules like the odontoblastic nuclei. The disruption of the odontoblastic layer and peripheral neural elements in the pulp with desiccation was also observed in a rat model using axonal transport of radioactive protein.
Biologic and Chemical irritation
Dental caries is clearly an infectious disease in which microorganisms and their virulence determinants constantly irritate the pulp, even at the early stages, long before pulp exposure. However, despite the elimination of visible caries during cavity preparation, the cavity floor is undoubtedly left with some contamination by caries bacteria. Although the rubber dam should be used with any cavity preparation to prevent cavity contamination with salivary microorganisms, the use of water coolants allows the cavity to be contaminated with bacteria from water lines. Concerns about residual cavity contamination prompted some to use cavity disinfection with caustic chemicals. Chemicals such as hydrogen peroxide, sodium hypochlorite, or calcium hydroxide solutions have been proposed for this purpose, although they may exert a toxic effect. An earlier study showed that the amounts of residual bacteria following adequate restoration are not significant. Once dentin is exposed, there is a constant outward flow of dentinal fluid that minimizes the inward flow of any noxious agents. This may aid in the reduction of irritation from residual microbial factors in dentinal tubules.
In contemporary practice, most chemical irritation during restorative procedures results from the application of etching agents, especially strong acids, in the form of total dentin etch, particularly if capping of exposed pulp is performed. Etching is performed to remove the smear layer, promote physical adhesion of bonding agents to dentin by forming resin tags in the dentinal tubules, and permeate the newer unfilled resin primers into the unmineralized surface layer of collagen to form the so-called hybrid layer.
If the cavity is relatively superficial and is adequately sealed with a restorative resin, then etching of dentin is probably not detrimental to the pulp because of the narrow diameter of dentinal tubules and their low density in peripheral dentin. In fact, one study documented that histologic evidence of bacteria in human cavities restored with composite was significantly less if the cavity had been etched with phosphoric acid than if it were etched with 17% EDTA or nonetched. Pulpal inflammation in this study was not correlated with the etching treatments but with bacterial presence; thus, in cases of etching with phosphoric acid, if bacteria were also present, severe pulpal inflammation and necrosis could be seen.
Self-etching formulations have become popular because they eliminate the separate etching step involved in total-etch procedures. Some have speculated that the bonding of self-etching systems may be poorer than total-etch systems because of the weaker acidity of the acidic primers of self-etching systems when compared to that of total-etch systems. However, studies have shown no significant differences between the two adhesive systems in postoperative sensitivity, long-term in vivo degradation, or long-term in vitro bond strength. One clinical study showed no differences between the two systems with respect to bacterial leakage and the inflammatory response in the pulp. The most important variable that affected the pulp in this study was the amount of bacterial leakage with either system.
Other factors that may contribute to pulpal irritation during resin placement from chemical/biologic irritants include unpolymerized monomer and polymerization shrinkage. Higher concentrations of monomeric resin components were shown to exert an inhibitory effect on T lymphocytes and spleen cells, and monocytes/macrophages in vitro. These components may leach directly into the pulp in deep cavities and cause chemical irritation. Shrinkage during polymerization of composites may induce internal stresses on dentin and create voids that allow microleakage. Shrinkage of resins is estimated to range from 0.6% to 1.4%, and should be minimized during placement by incremental curing and possibly starting the restoration with flowable resins.
In summary, the available evidence indicates that chemicals involved in modern restorative procedures may irritate the pulp if placed directly on an exposure, or if there is microbial leakage along the tooth/restoration interface.
The Proximity of the Restorative Procedures to the Dental Pulp and the Surface Area of Dentin Exposed
It has been known for several decades that as the carious lesion progresses toward the pulp, particularly when the remaining dentin thickness (RDT) is less than 0.5 mm, there is an increasingly severe pulpal reaction, with a greater likelihood of the pulp undergoing irreversible pathosis. The diameter and density of dentinal tubules increase closer to the pulp ( Fig. 13-17 ). Based on the dentinal tubule density at the DEJ (about 65,000/mm 2 ) and the pulp (about 15,000/mm 2 ), it was estimated that the area occupied by tubule lumina at the DEJ was 1% of the total surface area at the DEJ and 22% at the pulp. Thus, it is not surprising that several studies have shown that pulpal inflammation in response to restorative procedures increases with the reduction in RDT. One study examined the differential effects on the rat pulp of the preparation method, remaining dentin thickness, coolant, drill speed, conditioning with EDTA, and filling materials. Subsequent to the cavity preparations a tooth slice was obtained and maintained ex vivo as an organ culture for up to 2 weeks. The results showed that the remaining dentin thickness was the most important factor in pulpal injury.
With the passage of time following cavity preparation, there is reduction in the permeability of RDT. This may be due to rapid deposition of reactionary dentin, the migration of large proteins into the tubules, or the diminution of tubule diameter as dentin becomes more sclerotic. Using a primate model, it was shown that the basic rate of secondary dentin deposition was about 0.8 µm/day and that this rate increased to an average of 2.9 µm/day following restorative procedures. Interestingly, in this study dentin deposition was also more rapid next to shallow cavities than deep cavities ; however, another study showed that total reactionary dentin deposited was thicker in deeper and wider cavities.
Clinically, it has been observed that postoperative sensitivity is common with many restorative procedures. Following resin composite restorations on patients, it was shown that postoperative sensitivity was related to the depth of the cavity, but not to the presence or absence of liners or bases.
In addition to the depth or the width of a large cavity preparation, a crown preparation exposes more dentinal tubules to microbial or chemical irritation. During crown fabrication, there are added irritation factors such as length of time of the preparation, impression techniques, and the imperfect adaptation of temporary restorations, causing microleakage during the temporization period. Because of the precise engineering requirements of some restorations, some providers may be inclined to reduce the coolant during crown preparation steps such as finalizing the finishing lines. However, crown preparations without coolants have been shown to dramatically reduce pulpal blood flow in an animal model ( Fig. 13-18 ). There are few studies available on the direct effects of modern crown and bridge techniques on the pulp. However, some long-term outcome studies have documented that the incidence of pulp necrosis following crown placement ranges from 10% to 50%.
The Permeability of Dentin and the Odontoblastic Layer Between the Area Being Restored and the Pulp
The permeability of dentin plays an important role in the ingress of potential irritants to the pulp. It is clear from research done since the 1980s that dentin is not uniformly permeable and that permeability depends on factors such as the location within the same tooth, the age of the patient, and the presence of pathologic conditions such as dental caries. Fundamentally, the permeability of dentin depends on the collective sum of the permeability of individual tubules at a particular site in the tooth. The tubular diameter increases from about 0.6 to 0.8 µm close to the DEJ to about 3 µm at the pulp. Given that bacterial cells are about 0.5 to 1 µm in diameter, it is evident that in deep cavity preparations, particularly when total-etch procedures are employed, bacteria can migrate through the remaining dentin into the pulp.
With age the width of peritubular dentin increases, causing a reduction in tubular lumen or sclerosis. Caries causes demineralization in superficial dentin, which is associated with remineralization and the formation of caries crystals within the tubules of inner undemineralized dentin ( Fig. 13-19 ). This causes a decrease in permeability in dentin subjacent to the carious lesion and could be considered a protective mechanism, as it may delay the progress of the carious lesion.
It was shown that irritation from cavity preparation increased the permeability of the odontoblastic cell layer only at the site of the cavity preparation. In addition to the physical barrier to permeability and the production of reactionary or reparative dentin, the odontoblastic layer may, in fact, contribute to the host response of the dental pulp by expressing important inflammatory mediators or recognizing bacteria through Toll-like receptors.
The Age of the Patient (see also Chapter 26 )
Resting pulpal blood flow (PBF), as well as the changes in PBF in response to cold application, will decrease with age. Age may also be associated with reduction in pulpal neuropeptides. However, studies show no differences between young and old pulp in the regenerative capacity of odontoblast-like cells and in the presence of cells positive for class II major histocompatibility complex, heat shock protein 25, or nestin, when subjected to cavity preparation. An examination of young versus old normal human pulp showed that young pulp had increased expression of biologic factors related to cell differentiation, proliferation, and the immune response, whereas older pulp had increased factors related to apoptosis. These analyses cannot translate to the pulp’s ability to deal with irritation and its sequelae. Thus, the net result of the ability of the pulp to cope with external stimulation or irritation in humans with advancing age is not clear.
Pulpal Reactions to Restorative Materials
The effects of restorative materials on the dental pulp have been investigated and seem to relate directly to the permeability of the associated dentin. The degree of dentin permeability, however, is often variable and is governed by several factors including age and caries status. The most important variable in dentin permeability to restorative materials is the thickness of dentin between the floor of the cavity preparation and the pulp.
Given the importance of dentin permeability, there are direct pulpal effects of any given restorative material that are governed by the composition of the material and associated eluted or degraded products. Unbound components of resin materials and preparative agents such as acid etchants can affect the subjacent pulp by inducing an inflammatory response. The indirect effects of desiccation or demineralization of dentin as well as the direct effects of the material itself when in contact with pulpal tissue mediate this inflammatory response. Studies have shown that the certain cytotoxic components of resin monomers (e.g., triethylene glycol dimethacrylate and 2-hydroxyethyl methacrylate) readily penetrate dentin. Similarly, eugenol and components of Ledermix (triamcinolone and demeclocycline) have been shown to pass through dentin into the subjacent pulp. In vivo data show that these chemicals have an effect on the pulp; however, the effect seems to be short lived and, in the absence of bacteria, it is reversible.
The mechanisms whereby restorative materials exert an injurious effect on the dental pulp vary. Evidence exists that supports direct and, in some instances, prolonged cytotoxicity, stimulation of hypersensitivity reactions, or impairment of the host immune response to bacteria. Some of the components of resin restorations are released at cytotoxic levels after polymerization is completed, leading to chronic stimulation and a resultant prolonged inflammatory response. Furthermore, even subtoxic concentrations of certain agents are capable of eliciting allergic reactions in humans. Primates hyperimmunized with BSA showed significant pulpal damage with repeated antigenic challenge in class V cavity preparations, suggesting a role for antigen-antibody complex–mediated hypersensitivity in tissue destruction. In a separate study, exposure to dentin primers elicited a delayed-type hypersensitivity reaction in guinea pigs. These studies taken together present a compelling argument for immune-mediated pulpal tissue damage subsequent to exposure to restorative materials. Foreign body reactions have also been described in pulps containing extruded globules of resin material. Histologic examination of these pulps shows macrophages and giant cells surrounding the resin particles. Lastly, resin monomers have been shown to decrease the activity of immunocompetent cells in a dose-dependent manner in in vitro functional assays. Although all of these effects are documented, their extent and therefore morbidity on the dental pulp is speculative and doubtless does not act solely to effect pulpal demise. As previously noted, most restorative materials are placed adjacent to pulps that are previously compromised by bacterial insult, and disease, debridement, and restoration of the tooth have cumulative effects on the dental pulp.
Although pulpal irritation is largely considered to be a negative sequela, the irritant potential of certain restorative materials is central to their usefulness in restorative dentistry. Calcium hydroxide is one of the oldest and most widely used medicaments for stimulation of dentinal bridge formation subsequent to microscopic or gross pulpal exposure. The low-grade pulpal irritation that it induces is important for dentinal bridge formation in exposures. The degree of inflammation is dependent on the preparation of calcium hydroxide used. Aqueous suspensions of calcium hydroxide applied to exposed pulps cause superficial necrosis of pulpal tissue followed by low-grade inflammatory changes. Within 30 days the tissue subjacent to the necrotic zone has reorganized and resumed normal architecture. Hard-setting calcium hydroxide preparations as well as mineral trioxide aggregates are effective in eliciting dentinal bridge formation with a much smaller to nonexistent necrotic zone. This is preferable in vital pulp therapies such as the Cvek pulpotomy, where maintenance of the maximum amount of vital pulp tissue is desirable and the extent of pulpal inflammation is minimal ( Fig. 13-20 ). The irritation potential of calcium hydroxide across intact dentin is dependent on factors such as the remaining dentin thickness and permeability. Application of calcium hydroxide to intact dentin appears to induce sclerosis by promoting crystal precipitation within the tubules accompanied by reductions in permeability.