Multiple complex reactions involving attempts at repair and tissue breakdown may go on either asymptomatically or with pain ranging from mild to unbearable. Pulpitis, due to caries, has been described as an infection where the host reaction has the capacity to produce more damage than that caused simply by the effects of the microorganisms [29].

The outcome of the carious process, with or without pulp exposure, is subject to many variables. There are genetic factors involved in host response that are only now being elucidated. Age of the patient also plays a role in the capacity of tissue to respond to an insult. Prior dental experiences are also a factor. A tooth with periodontal disease and/or deep restorations often has a chronically inflamed pulp. Such a tooth is less likely to respond favorably to additional insults than a virgin tooth with healthy pulp and periodontal tissues. The clinician and his/her skills is also an important variable.

Pain, due to caries, is influenced by release of microbial metabolic products and growth factors from the dentin extracellular matrix. At the same time, the tubular characteristics of dentin and the extent of tubular sclerosis due to the reactionary response of the pulp-dentin complex affect the permeability of dentin. The degree of permeability affects the diffusion kinetics of the metabolic and degradation products into the pulp [31].

Necrotic pulp is a dead tissue without functioning vasculature or structural integrity. It provides an ideal culture medium for bacterial colonization. In some cases this process unfolds rapidly and in others very slowly. Pain associated with the process is unpredictable and ranges from virtually intolerable to painless. Clinicians may see large carious exposures of long duration that have caused no pain in contrast to small carious pulp exposures that are extremely painful.

Histologically, it is common to find, within the same pulp, areas of acute inflammation, chronic inflammation, and necrosis. This is a dynamic process and the exposed pulp should be considered a tissue with numerous outcome possibilities. It may proceed to necrosis with or without symptoms or remain as an asymptomatic or symptomatic vital tissue for an indeterminate period of time. A better endodontic outcome is likely if pulp pathosis is treated before periapical pathosis develops.

Sensibility tests of a tooth with a carious exposure should be considered within the context of a dynamic tissue undergoing change. It is well established that pain and sensibility testing are not predictors of the histologic state of the pulp. Despite a vital response of a tooth to pulp testing, it should not necessarily be considered a normal pulp. Exposures and traumatized teeth with partial necrosis may have enough viable neural tissue remaining, to respond to provocation, and mislead a clinician. Ultimately, bacteria in the root canal system results in pulp necrosis.

A classic study demonstrated the critical role of bacteria following a pulp exposure and the tissue’s reaction to the presence of bacteria. Using a rat model, it was found that in the presence of bacteria, pulp tissue became partially necrotic within 8 days and completely necrotic with formation of periapical abscesses by 14 days. This response was not seen in germ-free animals with pulpal exposures.

At 32 days after pulp exposure in germ-free rats, an intact dentin bridge developed with normal pulp tissue beneath the newly formed dentin. Thus, bacterial infection of the pulp is the key etiologic factor for pulp necrosis. Endodontic therapy must include materials and methods that significantly reduce or eliminate bacteria [22].

This classic study is central to our understanding of endodontic success and failure.

Clinical procedures must be judged in the context of their ability to diminish or eliminate bacteria in the root canal system.

Restorative procedures can be the cause of pulpal problems. An important issue is microbial microleakage [41]. Penetration of microbes into the deeper sections of dentin and pulp can cause severe pain that may be difficult to diagnose. The durability of bonding and clinical success of adhesive restorations is an important area for continued research [9]. Iatrogenic factors during restorative procedures such as inadequate coolant and generation of heat are also potential causes of pulpal breakdown.

It is common to have a patient complain of thermal sensitivity following a restorative procedure. A key question for the clinician involves determination of whether or not pulpitis and resulting thermal sensitivity is reversible or irreversible. The patient’s level of pain and its duration are subjective findings but are important factors in judging the probability of reversibility or irreversibility of the process.

The aim of the wise is not to secure pleasure but to avoid pain Socrates

Biologically based preoperative, intraoperative, and postoperative strategies can have a preventive effect on patient’s pain and endodontic experience. A pain-preventive or preemptive strategy is a multifaceted plan directed at prevention or reduction of intraoperative and postoperative pain. The strategy includes anxiety reduction, profound local anesthesia, biologically based operative and postoperative procedures, and preemptive use of analgesics.

Most clinicians have treated two patients of the same gender with similar teeth and medical/dental histories. The teeth are treated using the same clinical approach but one patient has a smooth postoperative course while another experiences complications including severe pain and swelling. The clinician often looks for an iatrogenic cause of the pain. While iatrogenic factors often exist, there is increasing evidence that there are other factors that may predispose some patients to complications.

This section will examine the potential role of predisposing factors and comorbidities including genetics, gender, and anxiety.

A comorbidity has been defined as a concomitant but unrelated pathologic or disease process [1].

For example, it has been suggested that patients with chronic pain conditions, elsewhere in the body, may be predisposed to prolonged pain after apparently successful endodontic therapy [40]. Patients with a high level of anxiety or chronic facial pain problems are examples of comorbidities that may affect the patient’s experience during and after endodontic therapy. A patient’s sex may also be a factor as there is evidence that females may be predisposed to certain painful conditions.

Although endodontic treatment can be virtually pain free during the procedure itself, some patients may experience varying degrees of pain following treatment. It is helpful for the clinician to recognize factors that are predictive of postoperative pain. That information may influence the endodontic treatment plan. For example, a decision concerning single or multi-visit treatment could be influenced by knowledge of predisposing factors [20].

Studies have investigated postoperative endodontic pain and reported an incidence of moderate to severe pain in the range of 15–25 % [10, 21, 37]. A prospective clinical study reported that 57 % of patients reported no pain after debridement and shaping of the root canal system, although 21 % had slight pain, 15 % had moderate pain, and 7 % had severe pain [17].

Although some patients may experience moderate to severe pain after endodontic treatment, few experience what is now commonly referred to as a flare-up or a postoperative problem requiring an unscheduled visit with unplanned treatment intervention to manage the patient’s symptoms [50]. Patients with a flare-up usually describe severe pain, swelling, or the sensation of pressure in their mandible or maxilla within 1 or 2 days of treatment.

The incidence of flare-up varies across studies and ranges from about 2 to 20 % of patients, with the higher prevalence generally reported in older studies using classic cleaning and shaping techniques [5, 46, 47]. Differences in experimental design prevent direct comparison of those research results, but the presence of preoperative pain or mechanical allodynia (reduced mechanical pain threshold or percussion sensitivity) was a positive predictor of postoperative pain in more than 15 studies involving more than 6,600 patients.

Other factors were more variable in their predictive value of postoperative pain. In a retrospective study, the dental records of 1,000 patients who had nonsurgical root canal treatment and experienced no flare-ups (i.e., unscheduled return visits) were compared with the records of 1,000 patients who experienced flare-ups after the cleansing and shaping of their necrotic root canals [45]. The results showed that factors such as presence of preoperative pain, tooth type, sex, age, history of allergy, and retreatment were significantly predictive for the incidence of flare-up, although intra-canal medicaments, systemic disease, and establishment of patency of the apical foramen had no significant relation to the incidence of flare-ups. Specifically, the highest incidence of flare-ups was associated with mandibular teeth, retreatment procedures, females over the age of 40, and patients with a history of allergies [45].

The role of genetics is an entirely new variable for dentists to consider. Genetics may play a role in predisposing some patients to a variety of complications including pain, poor healing, and abscess formation. Genetic factors may also be important in determining how a person responds to specific drugs. Considering the role of genetics in endodontics is highly complex and at an early stage of development.

Increasingly, current endodontic literature provides examples of how genetics may influence endodontic symptoms and outcomes. Findings suggest that specific markers associated with the pro-inflammatory regulator Il-1B, a key regulator of host response, may contribute to increased susceptibility to periapical pathosis [32]. It has also been suggested that genetic factors are associated with a susceptibility to develop symptomatic dental abscesses [11].

Numerous genes are involved with the pharmacokinetics and dynamics of opioids thus complicating the issue of genetics and patient’s response to an opioid. A variety of genetic polymorphisms clearly influence pain perception and behavior in response to pain. The response to analgesics differs depending on complex factors including the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration [49].

The Human Genome Project has contributed to the possibility of the development of drugs specific for individualized therapy. It seems clear that genetic variations influence both the efficacy and side effects of drugs used to treat pain. A study examined genetic and environmental contributions to variability in pain sensitivity and responsiveness to opioid analgesics. Findings indicated that interindividual variance in responsiveness to opioids is at least in part due to genetics [3]. More than 20 genes affecting pain sensitivity in humans or interindividual variability have been identified. While at this time some of the data is conflicting, it is exciting to think about what the future of genetics may mean to endodontists of the future [33].

For example, it has been suggested that markers in MMP3 and MMP2 genes could predict host susceptibility to developing periapical lesions and the healing response. Genetic predisposition in specific genes can contribute to persistent apical periodontitis [30]. It seems likely that an understanding of the genetic basis of endodontic pain perception will advance our pharmacologic management of postoperative pain.

These preliminary findings point to a rich complex of factors associated with patient’s pain and treatment outcomes. It is possible that as more information is collected, we will be better able to identify those patients predisposed to pain and have a diminished capacity for healing.