SP was the first neuropeptide to be detected in dental pulp. SP, CGRP and NKA coexist in the same nerve fibers in the pulp and originate from the trigeminal ganglion. (8)

Pulpal vasodilatation is markedly reduced after systemic administration of a specific SP antagonist or Somatostatin. Thus, Somatostatin, present in trigeminal nerve, inhibits the release of SP and reduces the concomitant vasodilation in the pulp following inferior alveolar nerve stimulation. (8)

CGRP is expressed in small to medium diameter sensory ganglion neurons whose central terminals lie in the superficial spinal and medullary dorsal horn. When extensive pulpal exposures were made on rat molars, the teeth exhibited an irreversible pulpitis, with complete necrosis of the pulp by 3-5 weeks post-injury. (8) Analysis of those teeth at various times post-injury shows persistent sprouting of CGRP-nerve fibers in the surviving vital pulp, and deformed nerve fibers at the vital / non-vital interface. (8) Silent pulpitis occur when fibrotic changes in the pulp form a barrier between the lesion and the nerve fibers. Coexistence of vital pulp and periapical lesions is caused by CGRP nerve sprouting and the effect of released neuropeptides on bone and periapical tissue.

Difficulty in acquiring anaesthesia in inflamed teeth is due to increased number of CGRP nerve fibers, which causes Ascending Neuritis. (9) CGRP due to its unique stimulatory effect on osteoblast proliferation inhibits bone resorption. (10)

VIP is a stimulator of bone resorption. Hohmann et al (1986) have shown that VIP stimulates bone resorption via Prostaglandin (PG)-E2-independent pathway and by enhancing the activity of undifferentiated osteoclasts. VIP also stimulates bone resorption by affecting osteoblast formation. (10)

Synthetic NPY exerts vasoconstrictor actions in the pulp in the low nanomolar range and, this effect is resistant to -adrenoceptor blockade. Compared to the effect of Noradrenaline (NA), Neuropeptide Y causes a more sustained vasoconstriction that lasts for several minutes after the end of an intra-arterial infusion. It is therefore plausible that NA and NPY act in concert in initiating and maintaining an appropriate vascular tone in the pulp. (8)

Neuropeptides play a vital role in hemodynamic regulation, orthodontic tooth movement of traumatized teeth, restorative procedures and tooth injury.

Dental Pulp is innervated by sensory neurons originating from the trigeminal ganglion (of which 80% of the nerves as C-fibers and the remaining are A-delta fibers). (11)

Although these neurons are classified as sensory (i.e., afferent) they have major efferent functions because of their release of neuropeptides (about 80% of SP) from their peripheral terminals. (12)

Activation of trigeminal sensory neurons induces pulpal vasodilation and increases pulpal blood flow, which produces plasma extravasation in the pulp. (8)

The association of calcitonin gene-related peptide and substance P with inflammation has been demonstrated via effects on blood flow (Brain et al., 1985; Kim et al., 1988), histamine release (Piotrowski and Foreman, 1986), and immune cell function (Payan et al., 1987; Lotz et al., 1988). Both substance P and calcitonin gene-related peptide, which are released from peripheral neurons in response to injury, contribute to the inflammatory response and also stimulate proliferation of surrounding connective tissue cells and thus initiate the early stages of healing in the pulp. (13)

Orthodontic tooth movement can cause degenerative and/or inflammatory responses in the dental pulp of teeth with completed apical formation. The impact of the tooth movement on the pulp is focused primarily on the neurovascular system in which the release of neuropeptides can influence both blood flow and cellular metabolism. (14) During tooth movement, release of Substance P (SP) causes pain perception and cellular recruitment in the pulp and alveolar bone remodeling in PDL. Studies have shown increased number of CGRP IR nerves in the pulp and periradicular tissues during tooth movement. Both A-delta and C fibers release various peptides by means of intra-axonal transport at the terminal nerve endings. When released, they act as neurogenic vasodilators and vasoconstrictors. Therefore these neuropeptides play an important role in the regulation of the blood flow to the pulp and the periodontium. The resultant increase in the blood flow to these tissues during tooth movement stimulates the osteoclast precursors to differentiate into osteoclasts and influence the resorptive remodeling process of the teeth. Thus, in endodontically treated teeth, due to the absence of neuropeptides the chances of resorption are less during orthodontic tooth movement, when compared to non-endodontically treated tooth as inferred by Bender in his extensive study. (15)

Situations like traumatic cavity preparation and exposed cervical dentin are invariably associated with rapid dentinogenesis, (16) which may be due to hydrodynamic activation, which release neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) in the pulp, where CGRP, increases the expression of bone morphogenetic protein (BMP). When this expression leads to more dentin formation, it also tends to lower dentin permeability by making the tubules longer. (17)

Injury to the pulpodentin complex produces numerous neuronal responses. The nerve fibers not only send rapid signals to the ganglion and central pain pathways, but they also release neuropeptides from the peripheral terminals. (18) Thus, if the sensory innervation has been removed prior to injury, the defense potential of the pulp to promote neurogenic inflammation or healing after pulpal exposure is considerably reduced. (19)

Injury can cause anatomic and cytochemical changes in the nerve endings. There is initial depletion of neuropeptides, followed by an increase in neuropeptide content and sprouting of terminal fibres within 1 day after injury. These responses differ in intensity and duration depending on the severity of the injury. (20)