An Introduction to the Brain Science of Dentistry: The Story of the Discovery of Mesencephalic Trigeminal Primary Neurons Innervating Tooth Pulp

Abstract

In 1994 we developed a useful new subject for the sixth-year dental students, "The Brain Science of Dentistry", which included lectures and laboratory practice concerning the relation between feeding and brain functions. As an example of the contents of the lectures, how dental pulp neurons were discovered in the mesencephalic trigeminal nucleus will be described.It has been generally accepted that the tooth pulp is supplied by small myelinated Aδ and unmyelinated C fibers, which elsewhere in the body are involved in nociception. However, several histological and physiological studies have shown the presence of a substantial proportion of pulpal afferents with conduction velocities and diameters which would be expected for Aβ processes. Additionally, a related structure, the periodontal ligament, has been demonstrated to receive a dual innervation from the trigeminal ganglion (TG) and the mesencephalic trigeminal nucleus (MTN). Based on these findings, we suspected the existence of afferent processes innervating the tooth pulp whose cell bodies are part of the MTN. We examined this possibility in the adult cat using retrograde axonal transport of horseradish peroxidase (HRP). There are at least two decisive problems to overcome if one is to demonstrate HRP-labeled tooth pulp neurons in the TG and MTN after depositing HRP in pulp chambers of the permanent teeth:(1) preventing an inhibition of axonal transport of HRP due to acute pulpitis following the surgical procedures required to apply HRP to pulp tissues, and (2) controlling leakage of HRP through the apical foramina into the surrounding periodontal tissues. To solve the first problem, prednisolone, an anti-inflammatory synthetic steroid, was given (5 mg/kg, i.m.) immediately after surgery and every 12 h throughout the survival period of 3 days. In all prednisolone-treated cats, a considerable number of labeled neurons were found in both the TG and MTN, ipsilaterally. On the other hand, no labeled neurons were observed in the MTN in cats receiving no steroids. To check the presence of HRP leakage, we used two techniques. All teeth injected with HRP and the surrounding alveolar bone were decalcified, sectioned serially, and processed using the TMB technique. Examination under dark-field illumination revealed no evidence of HRP spread as far distally as the apical foramina and periodontal ligaments. The HRP-gel implant method is considered to be easier for localizing the spread of HRP, compared to the fluid injection method. In two additional steroid-treated cats, 1μl of 30% HRP entrapped in 5% polyacrylamide gel was placed in the pulp horn of the mandibular left canine. This procedure resulted in the labeling of 10 and 13 MTN neurons in the respective cats. When the number of HRP-labeled tooth pulp neurons in the MTN and TG were compared among five different mammalian species (rats, rabbits, cats, dogs, and monkeys), a conspicuous species difference was found in the tooth pulp innervation by the MTN. In cats, dogs and monkeys, HRP-labeled neurons were found in both the TG and MTN, but no labeled neurons were counted in the MTN of rats and rabbits. In conclusion, dual innervation of the tooth pulp by the TG and MTN occurs in the cat, dog, and monkey, but not in the rat and rabbit. This species difference in pulpal innervation might be brought about by a cumulative dominance over the teeth closely associated with feeding habits.