An Interpretation of Dental Innervation Based upon the Pattern of Calcitonin Gene-Related Peptide (CGRP)-Immunoreactive Thin Sensory Axons

Abstract

Calcitonin gene-related peptide (CGRP) is a recently characterized neuroactive substance that is expressed in a large proportion of small- to medium-diameter sensory ganglion neurons whose central terminals lie in the superficial spinal and medullary dorsal horn. This restricted distribution within the peripheral nervous system suggests a prominent role for the peptide in nociceptive processing. The mammalian tooth pulp, which receives a relatively homogeneous afferent input from thin (putative nociceptive) fibers originating from this subpopulation of trigeminal ganglion cells, thus affords an ideal target zone in which to examine peripheral nociceptive mechanisms. The large percentage of these neurons displaying CGRP-like immunoreactivity (CGRP-LI) furthermore provides a valuable tool to study its thin-fiber afferent innervation. CGRP-LI has been localized within intact, decalcified specimens of rat, cat, monkey, and human teeth and associated dental structures. A remarkably robust CGRP-LI innervation of molar pulp and dentin was revealed in all species, with fibers coursing both in fascicles and individually, in variable relation to blood vessels and pulpal stroma. Our methods enabled tracing of a large number of axons through Raschkow's plexus and odontoblast layer into dentinal tubules. Paralleling anterograde axonal transport studies, a greater share of fibers was found in coronal vis-à-vis radicular dentin. In the rat, this fiber pattern stood in contrast both to incisor dentin, which appeared devoid of CGRP-LI, and to the abundant labeled axons in gingiva and periodontal tissues. Surgical deafferentation of rat mandible resulted in widespread depletion of CGRP-LI, while superior cervical ganglionectomy was without effect, confirming the sensory nature of the CGRP-LI fibers. Neonatal capsaicin treatment greatly attenuated the immunostaining, providing evidence for CGRP-LI localization in chemosensitive unmyelinated afferents. The great density of CGRP-LI axons demonstrated is considered in contrast to the restricted range and extent of sensory stimuli to which teeth are presumably subjected, and in relation to the diverse ongoing trophic, regulatory, and reparative processes in tooth structures. It is therefore suggested that these fibers may be subserving prominent efferent roles in dental pulp not directly related to nociception.

Immunoelectron Microscopic Observation of Calcitonin Gene-Related Peptide(CGRP)-positive Nerves in the Dental Pulp of Rat Molars.

“…The CGRP-containing nerve fibers distributed around blood vessels in the dental pulp are regarded as a type of nerve distinct from those involved in sensory transduction (SILVERMAN and KRUGER, 1987), although they are exclusively originated from trigeminal sensory neurons (SILVERMAN and KRUGER, 1987;WAKISAKA et al, 1987). In fact, CGRP is known to be a potent vasodilator , and acts as an enhancer of tachykinin-induced protein extravasation (BRAIN and WILLIAMS,1985;GAMSE and SARIA, 1985).…”

“…Recent immunohistochemical studies have revealed that nerve fibers in the dental pulp contain several neuropeptides including vasoactive intestinal polypeptide (VIP), substance P, and calcitonin gene-related peptide (CGRP) (UDDMAN et al, 1986;WAKISAKA et al, 1985;SILVERMAN and KRUGER, 1987). Among these neuropeptides, CGRP seems one of the most important because of its dense distribution in the dental pulp (HOSHINO et al, 1987;SILVERMAN and KRUGER, 1987).…”

“…Among these neuropeptides, CGRP seems one of the most important because of its dense distribution in the dental pulp (HOSHINO et al, 1987;SILVERMAN and KRUGER, 1987). Accordingly, immunohistochemistry for CGRP has been applied to investigate the neurophysiology of dental pulp, and suggested a possible role of CGRP as a vasoregulator in the dental pulp (UDDMAN et al, 1986;WAKISAKA et al, 1987).…”

A Light and Electron Microscopic Study on Pulpal Nerve Fibers in the Lower Incisor of the Mouse.

“…In contrast, some studies have showed sensory innervation in the rat incisor pulp by experimental studies involving cutting the trigeminal nerve (HIURA et al, 1973;SAKAI, 1974;KATAYAMA, 1982;KUBOTA et al, 1985), and by HRP-tracing method (FURSTMAN et al, 1975) and autoradiography (BYERS and KISH, 1976). Recently, the occurrence of sensory innervation of the rat incisor was demonstrated by immunohistochemistry for calcitonin gene-related peptides (CGRP), which are known to function as sensory neurotransmitters (SILVERMAN and KRUGER, 1987;MORI et al, 1990). MORI et al (1990) proved that these CGRP-positive nerve fibers are derived from medium to large sized neurons in the trigeminal ganglion, employing the injection of fast blue into the incisor pulp.…”

Changes in innervation of long bones after insertion of an implant: Immunocytochemical study in goats with antibodies to calcitonin gene‐related peptide and B‐50/GAP‐43

“…t has been well known for several decades that a role in bone remodeling, on the basis of the pattern bones and the surrounding soft tissues are innervated of innervation of molar teeth (45), the strong inhibitory (31,32). Immunocytochemistry has shown that differinfluence of CGRP on osteoclastic bone resorption ent chemically defined types of fibres are involved in the innervation of the skeleton (2, 3,7,12,13,19,22,31).…”