Mechanisms of Pain of Endodontic Origin

One might think the term odontalgia or toothache should describe a fairly homogenous clinical phenomenon. However, we now know that there are multiple etiologies for pain originating from teeth that include inflammation of the dental pulp, inflammation of periapical tissues, transdentinal stimulation of pulpal neurons, and even persistent pain after surgical intervention.

Nociceptive Pain

Nociceptive pain describes the inherent ability of pain fibers, or nociceptors, to detect stimuli that are potentially tissue damaging, and can be of a thermal, mechanical, or chemical nature. Nociceptive pain is mediated by smaller-diameter sensory afferents that include the myelinated A8- and unmyelinated C-fiber classes. The dental pulp appears to have a unique sensory capacity, as almost any stimulus that activates pulpal nerve endings produces the sensation of pain. The neural component of the pulp tissue consists of sensory trigeminal afferents and sympathetic and parasympathetic efferent fibers [10, 11]. These fibers project into the pulpal tissues of the root canals through the apical foramen and are closely associated with blood vessels, forming a collagen-bound neurovascular bundle. Anatomical studies have demonstrated that the terminal portion of pulpal afferents can extend up to 150 pm into the predentin or the dentinal tubules and form a close association with the processes of odontoblasts [12, 13]. These sensitive fibers act like nociceptors, in that they produce pain when stimulated. However, according to their diameter, conduction velocity, and expression of specific markers that identify classes of neurons, most of these fibers are large-diameter myelinated Ap-fibers, which typically transduce non-painful stimuli such as light touch [14-16]. This is an apparent paradox, as pain is thought to be exclusively mediated by the activation of A8- and C-fiber nociceptive afferents. In an attempt to explain this paradox, Fried and colleagues have proposed the novel term “algoneuron” to explain the observation that the pulp is innervated primarily by larger-diameter fibers that appear to, paradoxically, transduce painful stimuli [17].

Also found in the pulp are A5-fibers, which have a smaller diameter and slower conduction speed relative to the Ap-fibers. At this time it is not known whether these fibers have a distinct function from that of the Ap-fibers. Collectively the Ap- and A5-fibers respond to stimuli that would produce fluid movement in dentinal tubules such as drilling, sweet foods, cold air, and hypertonic solutions and produce a sharp, bright, pain when activated [18, 19]. The low threshold for activation and the peripheral localization of these fibers suggest that they can become activated and produce pain without the presence of irreversible damage to the pulp. These fibers contribute to the increased sensitivity observed after restorative work involving enamel and dentin removal or toothbrush abrasion (see Dentinal Pain Sect. [20].

Finally, the C-fiber subtype of sensory neurons, although less abundant, is are also found in the pulp. These are unmyelinated fibers with a low conduction velocity, a smaller diameter, and a higher excitation threshold. They are located deeper within the pulp than the myelinated fibers. C-fibers are activated by heat, mechanical, and chemical stimulation and produce a dull, diffuse, and longer-lasting pain [13]. It is thought that when C-fiber involvement produces pulpal pain, the patient reports a diffuse, dull, and achy pain that can be difficult to localize. This type of pain may suggest that concomitant damage to the pulp proper has occurred, which is more likely to be irreversible. While an injury results in an interruption in the pulp microcirculation, the C-fibers continue to function for a longer time compared to A-fibers as their oxygen consumption is higher than A-fibers [20]. This characteristic also underlines the familiar clinical occurrence in which a tooth that responds negatively to testing with a cold CO2 stick is painful to mechanical instrumentation during endodontic therapy [21].

The ability of a sensory neuron to detect specific types of stimuli is dictated by the receptors that are expressed in the peripheral terminal. Of particular relevance to the detection of painful thermal, mechanical, and chemical stimuli is the presence of transient receptor potential channels (TRPs) [22, 23]. The most-studied TRP channels are TRPV1, TRPV2, TRPA1, and TRPM8, all of which are expressed in pulpal afferents and thus have the potential to mediate thermal and mechanical sensation in the dental pulp (Fig. 6.1). For example, applying heat directly in the tooth produces pain, which is most likely mediated by activation of the TRPV1 channel [24, 25]. In addition to heat, A5- and C-fiber neurons also are responsive to noxious and non-noxious cold temperatures. Calcium imaging studies revealed that neurons responding to cold temperatures <18°C are more common in the trigeminal ganglion (14 %) than in the dorsal root ganglion (7 %) [26]. Both the TRPM8 and TRPA1 channels are stimulated by cold temperatures with thresholds of 25°C and 17°C, respectively, and both receptors have been localized in nerve fibers innervating the dental pulp [27, 28]. Further work is needed to determine whether TRPM8 and TRPA1 contribute to the transmission of painful cold in the dental pulp.

Molecular mechanisms of neural theory. Thermo-TRP channels are functionally expressed by dental primary afferents (Figure adapted from Chung et al. (2013) [22])

Fig. 6.1 Molecular mechanisms of neural theory. Thermo-TRP channels are functionally expressed by dental primary afferents (Figure adapted from Chung et al. (2013) [22])

The role of odontoblasts in transducing nociceptive pain in the dental pulp is an active topic of debate [29]. Importantly, odontoblasts also appear to express several of the TRP receptors, which support their role in detection of sensory stimuli [30, 31]. The mechanism transduction of sensory stimuli from odontoblast to peripheral nerve is not clear, and studies attempting to better understand these mechanisms are ongoing.

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