Reactionary Dentinogenesis and Neuroimmune Response in Dental Caries.

Reactionary dentin formation is an adaptive secretory response mediated by odontoblasts to moderate dentin injury. The implications of this process for neuroimmune interactions operating to contain pathogens have not been fully appreciated. The purpose of the present study was to describe the relationship between reactionary dentinogenesis, the neurogenic changes of dental pulp innervation, and dendritic cell recruitment to caries progression, using a comparative immunohistochemical approach in human teeth from young adult individuals. Reactionary dentin formation during dentin caries progression is associated with changes in the integrity of junctional complexes within the odontoblast layer. Diminished coexpression of Cx43 and zonula occludens 1 implies a reduced level of intercellular connectivity between odontoblasts. Dentin caries also causes overexpression of growth-associated protein 43, a modulator of neural plasticity that promotes extensive sprouting of nerve endings into the reactionary dentin matrix. At the same time, an elevated number of HLA-DR-positive dendritic cells infiltrate the odontoblast layer and subsequently invade reactionary dentin formed underneath the early caries-affected regions. Simultaneous odontoblast layer remodeling, nerve fiber sprouting, and activation of dendritic cells during caries progression suggest a coordinated neuroimmune response to fight caries pathogen invasion and to promote dentin-pulp healing. We propose that reactionary dentin formation hinders pathogen invasion and supports defensive neuroimmune interactions against infection. The eventual understanding of this complex scenario may contribute to the development of novel approaches to dental caries treatment.

Ultrastructural relation between nerve terminals and dentine bridge formation after pulpotomy in human teeth.

Close association between nerve terminals and preodontoblasts, odontoblasts and predentine was observed during healing after pulpotomy. The nerve terminals frequently contained large numbers of synaptic vesicles. Terminals with many vesicles tended to be fewer in the predentine than in the odontoblastic layer. The distribution of terminals was more dense at the stage before the regenerated odontoblasts became arranged regularly beneath the predentine. It is suggested that these terminals have some efferent role(s), especially during collagen synthesis at the early stage of dentinogenesis. The nerves may release their abundant synaptic vesicles, in addition to serving a sensory role for monitoring the increased sensitivity in the injured areas.

Effects of dental trauma on pulpal and periodontal nerve morphology.

Regeneration and morphological changes in sensory peptidergic nerves in pulp and periodontium were studied after general dental trauma by means of immunohistochemistry. In control teeth also the total nerve supply was demonstrated by using antibody to the general neuronal marker, protein gene product (PGP)9.5. Two experimental rat models were used, i.e. tooth replantation and induced traumatic occlusion. Results from these studies are reviewed here. In the controls, the PGP9.5-immunoreactive(IR) nerve supply in pulp and periodontium was generally denser compared to CGRP-IR and SP-IR nerves. In the replanted teeth, regeneration of CGRP-IR nerves closely followed the pulp cell renewal. Density and distribution of the regenerated nerves showed two different patterns which seemed to depend on the capacity of the renewed pulp to form postoperative dentine. The nerve density never reached the same level as the controls. In teeth not able to form irregular dentine, the pulp was sparsely innervated and the pulp cavity was filled with innervated bone. Nerve responses in CGRP-IR and SP-IR nerves after unilateral induced traumatic occlusion in the first maxillary molar were studied at different observation periods up to 30 days. After 5 days, localized morphological nerve changes were found both in the pulp and periodontium within the total rat molar dentition. With increasing observation periods, the pulpal neural changes progressed and were extended to all pulpal areas compared to the periodontium, where the nerve responses remained localized to cervical and apical tissues throughout the experiment.

Autoradiographic location of sensory nerve endings in dentin of monkey teeth.

We have used the autoradiographic method to locate trigeminal nerve endings in monkey teeth. The nerve endings were labeled in two adult female Macaca fascicularis by 20 hours of axonal transport of radioactive protein (3H-L-proline). We found a few labeled axons in contralateral mandibular central incisors and one mandibular canine. In ipsilateral teeth, numerous myelinated and unmyelinated axons were labeled; they formed a few terminal branches in the roots but primarily branched in the crown to form the peripheral plexus of Raschkow and to terminate as free endings in the odontoblast layer, predentin, and as far as 120 micrometers into dentinal tubules. Electron microscopic autoradiography showed that the radioactive axonally transported protein was confined to sensory axons and endings; odontoblasts and dentin matrix were not significantly labeled. Labeled free nerve endings were closely apposed to odontoblasts in dentin but did not form distinctive junctions with them. Nerve endings were most numerous in the regular tubular dentin of the crown adjacent to the tip of the pulp horn, occurring in at least half of the dentinal tubules there. Reparative dentin was poorly innervated, even near the tip of the crown, and it had a different tubular structure and adjacent pulpal structure from the innervated dentin. Radicular dentin was not innervated in most areas but did contain a few labeled axons where the predentin was wide and the odontoblasts were columnar, as at the buccal and lingual poles of some roots. Our results show tha dentinal sensory nerve endings in primate teeth can be profuse, sparse, or absent depending on the location and structure of dentin and its adjacent pulp. When dentin was innervated, the tubules were straight and contained odontoblast processes, the predentin was wide, the odontoblast cell bodies were relatively columnar, and there was an adjacent cell-free zone and pulpal nerve plexus.