From the synthesis of pain, through the pathophysiology of the pulpal organ, to the modern clinical systematization of the norm and pulpitis

Abstract

In scholarly literature, one may find classifications of pulpal pathology based on histomorphological and radiological criteria. These systematizations, as a rule, miss many several clinical variants, often leading to difficulties in choosing a treatment protocol.

Aim of the research: To evaluate the necessity of a modern classification of inflammatory pulp pathologies.

The medical history, especially the patient’s description of pain, is an important point in formulating the diagnosis and arguing in favour of the treatment plan.

The systematization of clinical-diagnostic categories, elaborated and proposed by the American Association of Endodontists (2008), addresses the health status of the pulpal organ – the “heart” of the tooth – and it fully complies with the requirements of practical dentistry, being unanimously appreciated by endodontists.

Key words: pulp pain, dental pulp, pulpitis, endodontic treatment.

Pain is present in most clinical forms of pulpitis, manifesting different features. Its characteristics differ significantly in comparison to other pathologies and it behaves differently in various forms of pulpitis, exhibiting specific signs of pain.

According to the International Association of The Study of Pain, pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. In general, pain is the manifestation of a defence mechanism, which informs one about the presence of disease, disorders in the functioning of an organ or the organism as a whole. Pain has a protective nature as long as it signals an imminent danger. However, if the pain keeps engaging the central nervous system, it gradually dulls the conscience, disorganising multiple bodily functions. [1, 19, 20]

A comprehensive classification of pain is beyond the scope of this review.

The subtle nuances of pain and its localisation in certain parts of the body are differentiated by the cerebral cortex.   The frontal lobe of the brain, which is connected by numerous associative projection fibresto other parts of the cortex,the thalamus and the limbic system, plays a part in the affective expression of pain. Pain cannot exist without consciousness. The unconscious person does not perceive pain! There is no “pain centre”,the entire cortex participating in the perception of pain. [1, 4, 5, 28]

In his classification of orofacial pain, Okeson places pulpal pain on axis I (physical condition)à somaticà deepà visceral pain. In the case of pulpitis, visceral pain appears to be caused by tissue ischaemia, with the subsequent accumulation of residual metabolites arising from the disruption of oxidative processes. This type of pain may be accompanied by local manifestations from the autonomic nervous system.[29, 32]

There are numerous theories of pain described in medical literature: [28]

1. The pain intensity theory – does not treat pain as a specific sensation, thus not admitting the presence of specific pain receptors. Excitants whose intensity approaches that of tissular aggression will generate a painful sensation regardless of the modality of the involved receptor.

2. The theory of the specificity of pain – treats pain as a specific sensation with its own receptor apparatus, pathways and specialised structures for analysing and integrating the information.

3. Contemporary theories of pain – predominantly based on the theory of the specificity of pain, but also considering the supraliminal stimulation of the receptors of any modality.

Specific pain receptors have been called nociceptors because they have a high stimulation threshold that would indicate the presence of noxious stimuli (lat. ‘destructive’ – nocens). In almost all regions of the body, these receptors have a higher density than otherreceptors, but the dental pulp is a special case, here reaching a density of 75,000 per cm². Nociceptive receptors adapt very slowly, which is why pain persists over time, keeping the individual aware of the presence of the noxious stimulus. Under certain conditions, the excitation of the pain nerve fibres may even increase progressively, leading to emetic pain.[28, 29]

The nerve fibres within the dental pulp that serve as nociceptors belong to two distinct classes according to structure, thickness and speed of nerve impulse transmission: [28, 29, 33]

• δ fibres – myelin fibres 2-5 μm thick, transmit nerve impulses at a speed of 3-30 m/s, specific to acute pain, lanceolate, well localised
• C fibres – myelin fibres 0.2-1.5 μm thick, transmit nerve impulses at a speed of 0.5-2.0 m/s, specific to dull pain, difficult to locate.

One can distinguish the following types of nociceptors: mechanonociceptors, thermonociceptors and chemonociceptors.[28]

Mechanonociceptors are stimulated upon movement of the cell membrane, leading to the depolarization of nerve endings. In most cases, the signals from these receptors are transmitted via A-δ fibres. The signals from thermoreceptors are transmitted in a similar fashion, being activated by high and low temperatures. [28]

Chemoreceptors are stimulated by various chemicals called algogens, which are released by damaged cells or in inflammatory foci. Algogensstimulate chemoreceptors while lowering the stimulation threshold for further stimuli. Algogens have been classified into three classes according to their origin:[28, 33]

• Tissular
  • Histamine
  • Prostaglandins
  • Acetylcholine
  • K⁺and Na⁺ions
• Plasmatic
  • Bradykinin
  • Kallidin
• Nervous origin
  • Substance P

Research has shown that administeringalgogenselicits a painful sensation.[33]

The pulp’s nociceptors associated with C-type fibres are sensitive to polymodal excitants: mechanical, thermal and chemical (both exogenous and endogenous). Thus, pain is generated by both external noxious stimuli and endogenous metabolic processes.[28]

Medical literature reveals a complex link between pain and pulpal inflammatory processes. Thus, not only are nociceptors activated in response to the inflammatory process, but the inflammatory process itself may be initiated and maintained by the activity of nociceptive fibres (the so-called neurogenic inflammation). Excitation of A-δ fibres would have an insignificant effect on pulpal blood flow, whereas excitation of C fibres causes an increase in blood flow, due to the release of neurokinins (SP, CGRP, NkA, ET-3). Substance P is released from the afferent fibres, causing vasodilation and contraction of endothelial cells, favouring plasma extravasation and mast cell degranulation, which release histamine that will exacerbate the vascular processes. Receptors for SP can be foundon the surface of lymphocytes, granulocytes and macrophages. Their activation will determine the release of pro-inflammatory cytokines IL-1, IL-6 and TNF, as well as PGE2 and thromboxane. Thus, the vicious cycle will ensue, perpetuating the inflammatory process and continually increasing pain sensitivity through the release of SP. Some studies also talk about the influence of neurokinins on parasympathetic fibres and them mediating the formation of tertiary dentine.[28, 31, 33]

Nerve signals from the receptors in the dental pulp reach the trigeminal ganglion via the A-δ and C fibres, where the protoneuron (first afferent neuron) is located. From there, the nerve fibres reach the neurons of the spinal tract of the trigeminal nerve (deuteroneuron), located in the medulla oblongata. From the medulla oblongata, part of the fibres go to the nuclei of the reticular substance and form the trigemino-reticulo-thalamic pathway, transmitting delayed, generalised pain. The other part of the fibres starts towards the neurons of the specific and non-specific nuclei of the thalamus, joining the ventral and dorsal trigeminothalamic tracts and ensuring the onset of immediate pain. The final relay of pain impulses is considered to be the thalamus, not the cortex.[28, 29]

The cortical cells that respond to tooth pulp excitation fall into two categories: [29]

• F (fast) neurons – short latent period. Information arrives via trigeminothalamic tracts whichterminating inthe neurons of the posterior ventro-medial nucleus of the thalamus, forming projections into the oral sensory area of the cortex;
• S (slow) neurons – long latent period. They are activated by trigemino-reticulo-thalamic pathways terminating in non-specific nuclei of the thalamus, forming vast thalamocortical projections.

According to literature findings, the sensation of primary epicritic pain might be formedin sensory zone I, due to a sensory-discriminative system that determines the quality, spatial location, intensity of dental pain and regulates the motor acts, which occur during the painful stimulus. Sensory area II receives information from the specific and non-specific nuclei of the thalamus and might participate in the formation of appropriate protective reactions and triggering mechanisms of the anti-nociceptive system.[28, 29, 34]

Modern theories of pain modulation describe three levels of pain control. [28, 29, 34]

The first level is formed by the structures of the midbrain and the medulla oblongata– the periapeductalgrey (PAG) and the raphe nuclei (RN). They have a non-selective descending inhibitory influence on trigeminal complex neurons (nociceptive as well as non-nociceptive). Simultaneous excitation of the reticular formation nuclei will limit the said inhibition only to nociceptive afferents.[28, 29, 34]

The second level of control involves the structures of the limbic system (hypothalamus and amygdala) through the selective inhibition of the reaction of neurons to nociceptive action. [28, 29, 34]

The third level of control of odontalgia could be found at the level of sensory area II, exerting top-down influences on the underlying antinociceptive structures.[28, 29, 34]

The nociceptive and antinociceptive mechanisms form a unitary system, the normal functioning of which is possible only when both subsystems maintain their activity. The antinociceptive system always exerts a tonic inhibition of the nociceptive system, and it has been shown that the action of the painful stimulus first inhibits the PAG-RN antinociceptive structures and then activates the nociceptive system. At the same time, the stronger the painful stimulus, the stronger the reaction of the antinociceptive system.[28, 29, 34]

The gate control theory (Melzack and Wall) explains the neural mechanisms of antinociception.

The spinal tract nucleus of the trigeminal nerve contains the extension of lamina II of the spinal cord, also known as the substantia gelatinosa of Rolando.  It contains local interneurons that participate in pain modulation, serving as a ‘pain gate’. Signals from myelinated fibres (type A fibres) activate the neurons of the substantia gelatinosa, while those from unmyelinated fibres (type C fibres) inhibit their activity. Excitation of the substantia gelatinosa causes presynaptic inhibition at the axonal ends of the first sensory neurons or postsynaptic inhibition at the corresponding second neuron. As a result, the flow of pain impulses to the overlying parts of the nervous system will decrease (the pain gate will close). When the substantia gelatinosa is inhibited, the opposite effect will occur: the transmission of nociceptive excitation will be facilitated (the pain gate opens). In this regard, the possibility of pain modulation by stimulating myelinated fibres, which in turn activate SG neurons, has been studied, and the antinociceptive effect of stimulating the proprioceptors of the masticatory muscles has been recorded.  The specific pain modulation mechanism operates under the control of the overlying parts of the nervous system, primarily the limbicoreticular complex and the cortex [2, 3, 4, 11, 26, 29].

Dental plexalgia has a varied array of clinical manifestations and depends on the involved plexus, the spread of the pathological process, the causal factors, the overall state of the organism.

The clinical picture of the disease will be dominated by severe, persistent pain, with severe syndromes and autonomous disorders. Usually, the pain would be localised around the pathological focus, with paroxysms lasting from several hours to several days, gradually diminishing in intensity. The course of the disease could also vary according to the characterological differences and past experiences of patients.

The pain can be constant or paroxysmal, with attacks lasting from a few minutes to several hours. Pain may be located in the upper or lower plexus with possible damage to both plexi. Plexalgia may be unilateral or bilateral.

The nature of pain in pulpitis directly depends upon the form of pulpal inflammation, which could be divided into two categories: acute (or exacerbation of a chronic form) and chronic.

In the initial stages, acute pulpitis is characterised by spontaneous, paroxysmal pain, either moderate or severe (the latter usually caused by thermal stimuli), with a long duration. The duration of a paroxysm is relatively short and the interval between them is relatively long. As the inflammation progresses, the paroxysms increase in duration, the intervals in between them getting shorter.

The advanced stages of pulpitis are characterised by diffuse inflammation, the patient suffering from spontaneous paroxysmal pain (more often at night). The induced pain is of considerable intensity, usuallycaused by cold stimuli. The pain is radiating, the patient indicating only the affected side, unable to locate the causal tooth.

With the exacerbation of chronic pulpitis, the pain exhibits the same features as the one from advanced acute pulpitis, with the only difference being prior pain in antecedents.

In the different forms of chronic pulpitis, the pain is mild and nagging, more often than not induced by causal factors (temperature fluctuations, the presence of food debris in the carious cavity etc.).

Referred pain is an important feature of pulpitis. The distant referred locations are described almost identically by most authors. For example, the pain from upper incisors will often radiate into the frontal region, the upper lip and the nose’s wings; from premolars and canines – upper lip, nose’s wings and the zygomatic region; first upper molar – temporal region; second and third upper molars – the meatus acusticus externus and the alveolar process of the mandible in the molar region; inferior incisors, canines and premolars – chin region; inferior molars – mandibular angle and the meatus acusticus externus; the third lower molar – submandibular and parietal regions. Sometimes the pain can radiate into the adjacent or even antagonist teeth. [11, 21, 22, 24, 26]

The differential diagnosis of dental plexalgia is not complicated. Plexalgia of pulpal origin is accompanied by a carious cavity in the causal tooth and exhibits  characteristic pain symptomatology.

The differential diagnosis could stick to the following flowchart [4, 11, 26, 29]:

• assessing the nature of the pain (paroxysmal or persistent);
• assessing the regions of referred pain (and whether it corresponds or not to the topography of the trigeminal nerve);
• assessing the pain spread (localised or diffuse);
• assessing the diurnal variations of pain;
• assessing the pain duration (seconds, minutes, hours or days);
• assessing the effect of masticatory pressure on the pain (the pain disappears or appears);
• assessing the influence of cold and hot thermal stimuli on the pain (the pain disappears or appears);
• assessing the influence of chemical stimuli on the pain;
• assessing the presence of trigger points (points that trigger a painful response upon touch).       

The variety of symptoms determined by the autonomous nervous system that accompany the attacks of pain are due to the connections between the nerve plexus and the autonomic ganglia (the pterygopalatine and the superior cervical ganglia). Table 1 contains information on the differential diagnosis between pulpitis and the neuralgia of the trigeminal nerve. [7, 8, 9, 10]

Table 1. Differential diagnosis between pulpitis and trigeminal neuralgia

If the presence of a carious cavity cannot be confirmed during clinical exam, one can use tests of thermal sensitivity (cold, hot etc.). Electrometric methods can be used to clarify the diagnosis, inflammation reducing the pulp’s electrical excitability, the minimal threshold surpassing 15-25 μA.

Another important aspect in the diagnosis of pulpitis was (and could still be) the radiographic exam, which allows one to visualise hidden cavities and their communication with the pulp chamber.

Our national medical training literature, similarly to many other countries on the globe, employs a systematisation of pulpal inflammatory pathology based on histomorphological and radiological criteria. The modern shift towards a whole body approach calls upon the introduction of a new, more rational systematisation of endodontic pathologies. For examples, Moldovan practitioners have long struggled with formulating diagnoses describing prior root canal treatments, prior unfinished root canal treatments etc.

In the Republic of Moldova, for a long time educational institutions and dental practices have used the classification of pulpitis formulated by N.A. Semashko of the Moscow State Institute of Dental Medicine (1968). The following classification addressed the criticism of previous classifications that complicated the formulation of a diagnosis, thus differentiating the following histopathological forms of pulpitis [24]:

1. Acute pulpitis: a) focal; b) diffuse

2. Chronic pulpitis: a)fibrous; b) gangrenous; c) hypertrophic

3. Exacerbated chronic pulpitis.

Based on its tenth revision of the ICD, the WHO formulated the „Application of the International Classification of Diseases to Dentistry and Stomatology”, where pulpal pathologies are coded using letters and arab numerals [24]:

K04 – Diseases of pulp and periapical tissues

K04.0 – Pulpitis;

K04.00 – Initial (hyperaemia)

K04.01 – Acute;

K04.02 – Suppurative (pulpal abscess);

K04.03 – Chronic;

K04.04 – Chronic, ulcerative;

K04.05 – Chronic, hyperplastic (pulpal polyp);

K04.08 – Other specified pulpitis;

K04.09 – Pulpitis, unspecified;

K04.1 – Necrosis of pulp.

              Pulpal gangrenae;

K04.2 – Pulp degeneration.

              Denticles

              Pulpal calcification

              Pulpal stones;

K04.3 – Abnormal hard tissue formation in pulp

              K04.3X – Secondary or irregular dentine

          Excludes: pulpal calcifications (K04.2)

                                               pulpal stones (K04.2)

There are also classifications based on other criteria, such as the DUILR (2011) classification rules [25](table 2).

Table 2. Pulpitis – classification criteria

In Romanian medical literature one can find a classification based on clinical and anatomo-topographical criteria [23]:

Preinflammatory hyperaemia

Acute pulpitis: serous (partial/total)

          suppurative (partial/total)

Chronic pulpitis: enclosed (actual enclosed pulpitis / enclosed hyperplastic pulpitis)

open (ulcerative/polypous)

Necrotising pulpitis

          Dystrophic diseases Pulpar dystrophies

          Pulpar gangrene

The four aforementioned classifications are based on histopathological criteria (perhaps also radiological), which is quite distant from the practical situations encountered in treating room and the practitioner’s day to day concerns.

Presently, the consensus classification proposed by the American Association of Endodontists (2008) could serve as a gold standard, thanks to its ease of application and it being a clinical compendium of endodontic practice, where the description of pain has an important role. For the reasons outlined above, the dental community uses this classification to present their case studies to an international audience.

The main goal when formulating a diagnosis concerning the dental pulp is to translate it into a proper, well argued clinical treatment. In 2008, the AAE convened to draft a consensus in the clinico-practical diagnosis formulation and the terminology concerning the health status of the dental pulp.

The AAE has devised the following necessary points in assessing the health status of the dental pulp [12, 13, 14, 15, 17]:

History of present disease: prior treatment, drug therapy

Chief complaints: since when, symptoms, duration of pain, location, onset conditions,  relief, referred or not, drugs.

Clinical exam: periodontal status, caries, direct restorations

Clinical tests:

          pulp tests: Endo Frost, heat test, electric pulp test

          periapical tests: percussion, palpation, biting

          other tests (if needed): transillumination, selective anesthesia

Radiographic analysis: periapical or bitewing Rx, CBCT.

The clinical health states of the dental pulp (AAE, 2008), where differentiation is made using morphological, functional and clinical criteria, with a thorough description of the experienced pain:

Normal pulp is a clinical diagnostic category in which the pulp exhibits no sympoms and is normally responsive to pulp testing. A histologically abnormal pulp may still yet be “clinically” normal, resulting in a mild or transient response to thermal cold testing, lasting no more than 1-2 seconds after the stimulus is removed. A correct diagnosis requires comparing the tooth in question with adjacent and contralateral teeth.

Reversible pulpitisis a diagnosis based upon findings (both subjective and objective) indicating that the inflammation should subside, with the pulp returning to normal following appropriate management of the aetiology. The patients experiences discomfort when a cold or sweet stimulus is applied, which then subsides no later than 10 seconds after the stimulus is removed. The typical etiologies are: caries, exposed dentin with dentinal sensitivity or deep restorations. There is no spontaneous pain. After having resolved the etiology (caries restoration or covering the exposed dentin), the tooth shall be further evaluated to assess whether the pulp has returned to a normal status.

Symptomatic irreversible pulpitis is a diagnosis based on findings (subjective and objective) that the still vital inflamed pulp is incapable of healing. The cold thermal test will result in sharp or dull pain, either localised or diffuse, lasting up to 30 seconds. Spontaneous (unprovoked) bouts of pain can also occur, as well as referred pain. Postural changes may affect the experience of pain (positively or negatively). Pain killers do not take the pain away. Likely causes comprise: deep caries, extensive restorations and fractures with pulp denudation. This condition requires root canal treatment.

Asymptomatic irreversible pulpitis is a diagnosis based on findings (subjective and objective) that the still vital inflamed pulp is incapable of healing. There are no clinical symptoms and usually the pulp responds normally to thermal tests. There is a communication between the carious cavity and the pulp chamber. This condition requires root canal treatment.

Pulp necrosis is a diagnostic category characterised by complete lack of vital signs from the pulp, indicating its death. Unless the root canal is infected, the tooth exhibits no signs of apical periodontitis. The patient may also simply not respond to thermal testing on any teeth, which is why the tests should be done comparatively.

Previously treated tooth is a clinico-therapeutical category stating that the tooth has been endodontically treated and its canals are obturated with a filling material. The tooth does not reacting to thermal testing.

Previously initiated therapy is a diagnostic category stating that that the tooth has been subjected to partial endodontic therapy (pulpotomy, pulpectomy). Depending on the level of therapy, the tooth may or may not be responsive to pulp tests. The finalisation of the treatment is strongly advised.

The systematization of clinical-diagnostic categories, elaborated and proposed by the American Association of Endodontists (2008), addresses the health status of the pulpal organ –  the “heart” of the tooth – and it fully corresponds to the requirements of practical dentistry, being unanimously appreciated by endodontists.