Cohen's Pathways of the Pulp 12th Edition PDF

522 PART II Advanced Science Topics The Trigeminal System includes both afferent neurons, which conduct sensory im- pulses, and autonomic or efferent neurons,165 which...

522 PART II Advanced Science Topics The Trigeminal System includes both afferent neurons, which conduct sensory im- pulses, and autonomic or efferent neurons,165 which provide INNERVATION neurogenic modulation of the microcirculation, inflamma- tory reactions,150 and perhaps regulate dentinogenesis.47 Pain is a subjective phenomenon involving not only sensory The sympathetic innervation of teeth derives from the physiologic responses, but also emotional, conceptual, and superior cervical ganglion (SCG).8,307 Postganglionic sym- motivational aspects of behavior. The existence of periph- pathetic nerves travel with the internal carotid nerve, join eral “nociceptive” (pain-detecting) sensory neurons forms the trigeminal nerve at the ganglion, and supply teeth and the basis for pain, and pain sensations of varying qualities supporting structures via the maxillary and mandibular and intensities are evoked by activation of the intradental division of the trigeminal nerve.244 Sympathetic fibers ap- nerves innervating teeth. Noxious stimuli in teeth are pear with blood vessels at the time the vascular system is transmitted in primary afferent neurons located in the tri- established in the dental papilla.106 In the adult tooth pulp, geminal ganglion via second-order neurons in the brain sympathetic fibers form plexuses, usually around pulpal stem to the brain (Fig. 13.13) (see also Chapter 4 and later arterioles (Fig. 13.14). Stimulation of these fibers results in in this chapter). Transmission of sensory information con- constriction of the arterioles and a decrease in blood sists of a cascade of events involving input, processing, and flow.1,82 The sympathetic neuron terminals contain the sensing,335 so the control of dental pain should be based on classic neurotransmitter, norepinephrine (NE), and neuro- an understanding of the origin of pain signals and the com- peptide Y (NPY) (see Neuropeptides later in this chapter). plex modulation that may take place locally and at higher NPY is synthesized in sympathetic neurons and supplied to levels. The sensory system of the pulp appears to be well terminals by axonal transport. By contrast, NE is mainly suited for signaling potential damage to the tooth. The produced locally in the terminals. Compared with the sen- tooth is innervated by a large number of myelinated and sory nerves, these fibers are most often located in deeper unmyelinated axons. The number of axons entering a hu- parts of the pulp proper, but fibers have also been found in man premolar may reach 2000 or more, and each axon close relation to odontoblasts.1,166 can arborize to form multiple points of innervation.92,171,172 The presence of parasympathetic cholinergic nerves in Regardless of the nature of the sensory stimulus (i.e., ther- dental tissues has been and is still controversial, although it mal, mechanical, chemical, electric [e.g., pulp tester]), almost has been concluded that there is absence of parasympathetic all afferent impulses generated from pulp tissue result in the vasodilation in the cat dental pulp.292,329 It has been reported sensation of pain. However, when the pulp is weakly stimu- that the neuropeptide vasoactive intestinal polypeptide (VIP) lated by an electric pulp tester under carefully controlled ex- is localized in the parasympathetic neurons.229,230 The origin perimental conditions, a nonpainful sensation (i.e., prepain) of VIP-containing fibers in the pulp is uncertain insofar as no has been reported.252 Thus not all afferent neurons that in- form of surgical denervation has resulted in complete loss of nervate the pulp are nociceptors. The innervation of the pulp these fibers from the dental pulp.397 Cortex Dura Thalamus Trigeminal ganglion Eye Sinus TMJ Tooth Spinal tract nucleus Muscle Skin Fig. 13.14 ​Histologic section, immunohistologically stained for neuro- peptide Y (NPY), shows the distribution of sympathetic nerves in the Fig. 13.13 ​Schematic drawing illustrating the convergence of sensory root pulp of a rat molar. NPY fibers are seen associated with blood ves- information from teeth to higher brain centers. TMJ, Temporoman- sels. (Courtesy Dr. Inge Fristad, Department of Clinical Dentistry, University dibular joint. of Bergen.)  13 Structure and Functions of the Dentin-Pulp Complex 523 Sensory nerve fibers are usually classified according the central region of the pulp (Fig. 13.17). Most of the un- to their diameter, conduction velocity, and function myelinated C fibers entering the pulp are located within (Table 13.1). The pulp contains two types of sensory nerve these fiber bundles; the remainder is situated toward the fibers: myelinated (A fibers) and unmyelinated (C fibers). It periphery of the pulp (see Fig. 13.15).313 It should be noted has been shown that there is some functional overlap be- that single neurons branch and innervate the pulps of mul- tween pulpal A and C fibers, as both fiber types can be noci- tiple teeth in animal studies.157 Assuming a similar innerva- ceptors.165,171,172,251,272 The A fibers include both A-b and tion pattern in humans, such organization may contribute A-d fibers. The A-b fibers may be slightly more sensitive to to the poor localization of dental pain and may also allow stimulation than the A-d fibers, but functionally these fibers neurogenic vasodilation and inflammatory reactions to are grouped together in the dental pulp, because both in- nervate the dentinal tubules, and both are stimulated by dentinal fluid movement (Fig. 13.15). Approximately 90% Location of Intradental Sensory Nerves of the A fibers in dental pulp are A-d fibers.251 Table 13.2 summarizes the principal characteristics of the main sen- sory fibers. During the bell stage of tooth development, “pioneer” nerve fibers enter the dental papilla following the path of blood vessels.106 Although only unmyelinated fibers are observed in the dental papilla, a proportion of these fibers are probably A fibers that have lost or not developed their myelin sheath. Myelinated fibers are the last major struc- tures to appear in the developing human dental pulp.11 The number of nerve fibers gradually increases, and branching occurs as the fibers approach dentin. During the bell stage, A-fibers, myelinated very few fibers enter the predentin.106 C-fibers, unmyelinated The sensory nerves of the pulp arise from the trigeminal Fig. 13.15 ​Schematic drawing illustrating the location of A and C fibers nerve and pass into the radicular pulp in bundles by way of in the dental pulp. Myelinated A fibers are located in the periphery of the foramen in close association with arterioles and venules the pulp, penetrating the inner part of dentin. Unmyelinated C fibers (Fig. 13.16). Each of the nerves entering the pulp is invested are located in the deeper part of the pulp proper. within Schwann cells, and the A fibers acquire their myelin sheath from these cells. With the completion of root devel- opment, the myelinated fibers appear grouped in bundles in Table 13.1 Classification of Nerve Fibers Conduction Type of Fiber Function Diameter (mm) Velocity (m/s) A-a Motor, 12–20 70–120 proprioception A-b Pressure, touch 5–12 30–70 A-g Motor, to muscle 3–6 15–30 spindles A-d Pain, temperature, 1–5 6–30 touch B Preganglionic ,3 3–15 autonomic Fig. 13.16 ​Histologic section, immunohistologically stained for calci- C dorsal root Pain 0.4–1 0.5–2 tonin gene-related peptide (CGRP), shows distribution of sensory nerves in the apical area of a rat molar. Nerve fibers are seen associ- Sympathetic Postganglionic 0.3–1.3 0.7–2.3 ated with blood vessels and enter the dental pulp in nerve bundles. sympathetic (Courtesy Dr. Inge Fristad, Department of Clinical Dentistry, University of Bergen.) Table 13.2 Characteristics of Sensory Fibers Fiber Myelination Location of Terminals Pain Characteristics Stimulation Threshold A-d Yes Principally in region of Sharp, pricking Relatively low pulp-dentin junction C No Probably distributed Burning, aching, less bearable Relatively high, usually associated throughout pulp than A-d fiber sensations with tissue injury 524 PART II Advanced Science Topics than 100 myelinated axons were present. Five years after eruption, the number of A fibers gradually increased to more than 700. The relatively late appearance of A fibers in the pulp may help to explain why the electric pulp test tends M to be unreliable in young teeth, as A fibers are more easily electrically stimulated than C fibers.110 M A quantitative study of axons 1 to 2 mm coronal to the root apex of fully developed human canine and incisor teeth172 reported a mean of about 360 myelinated axons in canines and incisors, whereas there were 1600 to 2200 M unmyelinated axons. However, this does not reflect the ac- U tual number of neurons supporting a single tooth, because multiple branching of the axons may occur in the periph- eral tissues. Overall, approximately 80% of the axons were M M unmyelinated fibers.171,172 The nerve bundles pass upward through the radicular Fig. 13.17 ​Electron micrograph of the apical pulp of a young canine pulp together with blood vessels. Once they reach the coro- tooth, showing in cross section myelinated nerve axons (M) within nal pulp, they fan out beneath the cell-rich zone, branch Schwann cells. Smaller, unmyelinated axons (U) are enclosed singly into smaller bundles, and finally ramify into a plexus of and in groups by Schwann cells.  (Courtesy Dr. David C. Johnsen, School single-nerve axons known as the plexus of Raschkow of Dentistry, Case Western Reserve University.) (Fig. 13.19). Full development of this plexus does not occur until the final stages of root formation.92 It has been esti- mated that each axon entering the pulp sends at least eight occur in an area of tissue wider than that affected by the branches to the plexus of Raschkow. There is prolific original insult (Fig. 13.18). This phenomenon, also known branching of the fibers in the plexus, producing a tremen- as the axon reflex,328 was first demonstrated in rat teeth and dous overlap of receptor fields.145,272,273,274,278 It is in the later confirmed in cat teeth where stimulation of a second plexus that the A fibers emerge from their encircling premolar caused neurogenic inflammation in the canine Schwann cells and branch repeatedly to form the subodon- tooth.157,199 An alternative explanation to this clinical ob- toblastic plexus. Finally, terminal axons pass between the servation is that the pulp has a relatively low density of odontoblasts as free nerve endings (see Figs. 13.19–13.21). proprioceptors, and thus patients have difficulty identifying The extent to which dentin is innervated has been the sub- the inflamed tooth until the inflammation reaches the peri- ject of numerous investigations.43,46,47,50,92,219 With the ex- radicular tissue, which is highly innervated with proprio- ception of the innervation of dentinal tubules, discussed ceptors. This is discussed in greater detail in Chapter 4. later in this chapter, the bulk of dentin is devoid of sensory In the human premolar, the number of unmyelinated nerve fibers. This offers an explanation as to why pain- axons entering the tooth at the apex reached a maximal producing agents (e.g., potassium chloride) do not always number shortly after tooth eruption.172 At this stage, an elicit pain when applied to exposed dentin. Similarly, appli- average of 1800 unmyelinated axons and more than 400 cation of topical anesthetic solutions to dentin does not myelinated axons were found, although in some teeth fewer decrease its sensitivity. Hence a high concentration of lido- caine solution is needed to block the response of intradental nerves to mechanical stimulation of the dentin.4 One investigator133 studied the distribution and organi- zation of nerve fibers in the dentin-pulp border zone of hu- man teeth. On the basis of their location and pattern of branching, several types of nerve endings were described (Fig. 13.22). Some fibers were found running from the subodontoblastic nerve plexus toward the odontoblast layer. However, these fibers do not reach the predentin; they terminate in extracellular spaces in the cell-rich zone, the cell-poor zone, or the odontoblast layer. Other fibers extend into the predentin and run through a dentinal tubule in close association with an odontoblast process. Most of these intratubular fibers extend into the dentinal tubules for only a few micrometers, but a few may penetrate as far as 100 mm (see Figs. 13.19 and 13.20). The area covered by a single such terminal complex often reaches thousands of square micrometers.133,273 Fig. 13.18 ​Branches of a single nerve fiber may innervate more than a single tooth. Nerve fiber activation in one tooth may thus result in Intratubular nerve endings are most numerous in the neurogenic inflammation in adjacent teeth innervated by the same area of the pulp horns, where as many as 40% of the tu- axon. The mechanism is known as the axonal reflex. This phenomenon bules may contain fibers.47,219 The number of intratubular may also contribute to the poor localization of pain reported by fibers decreases in other parts of the dentin, and in root patients. dentin only about 1% of dentinal tubules contain fibers.  13 Structure and Functions of the Dentin-Pulp Complex 525 D D OB dt C D * dt P dt D OB OB A B D Fig. 13.19 ​Histological sections from a human premolar labeled with the neurochemical marker protein gene product (PGP) 9.5, showing the dental pulp and surrounding dentin. A, Nerve fibers entering the coronal pulp (P) form a dense network beneath the odontoblasts (OB), known as the plexus of Raschkow (*). B, Nerves are entering the apical area and pass through the radicular pulp as nerve bundles (arrows). Attached and free denticles (dt) are seen close to dentin in the apical area. C and D, Compared to dense peripheral branching of nerves in the coronal pulp (C), the branching of nerves in the radicular pulp is sparse (D). (Courtesy Dr. Inger Hals Kvinnsland.) NF PD O O Fig. 13.21 ​Unmyelinated nerve fiber (NF) without a Schwann cell cov- ering located between adjacent odontoblasts (O) overlying pulp horn of a mouse molar tooth. Predentin (PD) can be seen at upper right. Within the nerve, there are longitudinally oriented fine neurofilaments, microvesicles, and mitochondria. (From Corpron RE, Avery JK: The ultra- structure of intradental nerves in developing mouse molars, Anat Rec 175:585, 1973.) This notion has been challenged in a study that stained pulps for protein gene-product 9.5, a specific marker for Fig. 13.20 ​Histologic section, immunohistologically stained for calci- tonin gene-related peptide (CGRP), shows the distribution of sensory nerves.235 In that study, root dentin appeared to be as well nerves in a rat molar. Nerves enter the coronal pulp in bundles and innervated as coronal dentin. The anatomic relationship ramify in a network beneath the odontoblasts (i.e., plexus of Rasch- between the odontoblast processes and sensory nerve end- kow), before entering between the odontoblasts and the inner part of ings has led to much speculation as to the functional rela- dentin. tionships between these structures, if any.46 When present, 526 PART II Advanced Science Topics pulpal A fibers.83 The excitability of C fibers is less affected D than that of A fibers by a reduction in blood flow.370 PD OP Of clinical interest is the evidence that nerve fibers of the OL pulp may be resistant to necrosis83,260 because their cell Fb bodies are found in ganglia outside the pulp. Because nerve bundles in general are more resistant to autolysis than other tissue elements, even in degenerating pulps, C fibers might still be able to respond to noxious stimulation. It may A B be that C fibers remain excitable even after blood flow has been compromised in the diseased pulp, as C fibers are often able to function in the presence of hypoxia.370 This may explain why instrumentation of the root canals of appar- ently nonvital teeth sometimes elicits pain. On the other hand, histologic studies on nonvital teeth failed to demon- strate high levels of innervation, leading to the suggestion that pain may be due to the transfer of noxious chemicals to terminals located in periapical tissues.260 C D Fig. 13.22 ​Schematic drawing showing distribution of nerve fibers in the dentin-pulp border zone. A, Fibers running from the subodonto- blastic plexus to the odontoblast layer. B, Fibers extending into the dentinal tubules in the predentin. C, Complex fibers that branch exten- sively in the predentin. D, Intratubular fibers extending into the dentin. D, Dentin; Fb, fibroblast; OL, odontoblast layer; OP, odontoblast pro- cess; PD, predentin. nerve fibers lie in a groove or gutter along the surface of the odontoblast process, and toward their terminal ends they twist around the process like a corkscrew. The cell mem- branes of the odontoblast process and the nerve fiber are closely approximated and run closely parallel for the length of their proximity, but they are not synaptically linked.162 Although it may be tempting to speculate that the odon- toblasts and their associated nerve axons are functionally interrelated and that together they play a role in dentin sensitivity, there is a paucity of evidence supporting this hypothesis. If the odontoblast were acting as a classic re- ceptor cell,† it would have chemical, electric, or mechanical communication with the adjacent nerve fiber. However, researchers have been unable to find classic anatomic structures (e.g., synaptic junctions) that could functionally couple odontoblasts and nerve fibers together. With regard to the membrane properties of odontoblasts, it has been reported that the membrane potential of the odontoblast is low (224 to 230 mV),202,231 and that the cell does not re- spond to electric stimulation.292,413 It would appear that the odontoblast does not possess the properties of an excitable cell. Further, the sensitivity of dentin is not diminished after disruption of the odontoblast layer.38,220 It is still possible that odontoblasts could modulate neuronal function via alteration in sodium channel activity or the release of para- crine factors that diffuse to the closely approximated nerve terminal. Another study showed that a reduction in pulpal blood flow (PBF), induced by stimulation of sympathetic fibers leading to the pulp, results in depressed excitability of