neuropeptide-y and Pulpitis

Dental pulp is a soft mesenchymal tissue densely innervated by afferent (sensory) fibers, sympathetic fibers, and parasympathetic fibers. This complexity in pulp innervation has motivated numerous investigations regarding how these 3 major neuronal systems regulate pulp physiology and pathology. Most of this research is focused on neuropeptides and their role in regulating pulpal blood flow and the development of neurogenic inflammation. These neuropeptides include substance P, calcitonin gene-related peptide, neurokinin A, neuropeptide Y, and vasoactive intestinal polypeptide among others. The purpose of this article is to review recent advances in neuropeptide research on dental pulp, including their role in pulp physiology, their release in response to common dental procedures, and their plasticity in response to extensive pulp and dentin injuries. Special attention will be given to neuropeptide interactions with pulp and immune cells via receptors, including studies regarding receptor identification, characterization, mechanisms of action, and their effects in the development of neurogenic inflammation leading to pulp necrosis. Their role in the growth and expansion of periapical lesions will also be discussed. Because centrally released neuropeptides are involved in the development of dental pain, the pain mechanisms of the pulpodentin complex and the effectiveness of present and future pharmacologic therapies for the control of dental pain will be reviewed, including receptor antagonists currently under research. Finally, potential clinical therapies will be proposed, particularly aimed to manipulate neuropeptide expression or blocking their receptors, to modulate a variety of biologic mechanisms, which preliminary results have shown optimistic results.

Topics: Alveolar Bone Loss; Animals; Calcitonin Gene-Related Peptide; Dental Pulp; Humans; Neurogenic Inflammation; Neurokinin A; Neurons, Afferent; Neuropeptide Y; Neuropeptides; Pulpitis; Substance P; Toothache; Vasoactive Intestinal Peptide

Recent findings have indicated that immune responses are subjected to modulation by the sympathetic nervous system (SNS). Moreover, the findings show that the SNS inhibits the production of pro-inflammatory cytokines, while stimulating the production of anti-inflammatory cytokines. The present review is an attempt to summarize the current results on how the SNS affects inflammation in dental tissues. In dental tissues, it has been found that the SNS is significant for recruitment of inflammatory cells such as CD 43+ granulocytes. Sympathetic nerves appear to have an inhibitory effect on osteoclasts, odontoclasts, and on IL-1alpha production. The SNS stimulates reparative dentin production, since reparative dentin formation was reduced after sympathectomy. Sprouting of sympathetic nerve fibers occurs in chronically inflamed dental pulp, and neural imbalance caused by unilateral sympathectomy recruits immunoglobulin-producing cells to the dental pulp. In conclusion, this article presents evidence in support of interactions between the sympathetic nervous system and dental inflammation.

Topics: Animals; Cytokines; Dental Pulp; Dentin, Secondary; Granulocytes; Humans; Interleukin-1; Leukosialin; Neuropeptide Y; Pulpitis; Sympathectomy; Sympathetic Nervous System

Blood flow of mammalian dental pulp is under both remote and local control. There is evidence for the existence of parasympathetic nerves in the pulp, but functionally the cholinergic influence is weak, and the physiological significance of this autonomic system seems to be low. The evidence for sympathetic vasoconstrictor nerves in the pulp is robust, and there is convincing support for the contention that these nerves play a physiological role, operating via release of noradrenaline and neuropeptide Y. However, there is no significant functional evidence in support of sympathetic beta-adrenoceptor-mediated vasodilation in the pulp. The local control of blood flow involves a subset of intradental sensory nerves. By virtue of their neuropeptide content, these afferent fibers cause vasodilation and inhibit sympathetic vasoconstriction in response to painful stimulation of the tooth. Such locally governed control may serve to meet immediate demands of the pulp tissue. A locally triggered reflex activation of sympathetic nerves in the pulp may modulate this control and limit its magnitude. Thus, there are competitive interactions between local and remote vascular controls which may be put out of balance in the injured and inflamed dental pulp.

Topics: Animals; Autonomic Nervous System; Cholinergic Fibers; Dental Pulp; Humans; Mammals; Neurons, Afferent; Neuropeptide Y; Norepinephrine; Parasympathetic Nervous System; Pulpitis; Receptors, Adrenergic, beta; Regional Blood Flow; Sympathetic Nervous System; Toothache; Vasoconstriction; Vasoconstrictor Agents; Vasodilation

To quantify the expression of calcitonin gene-related peptide (CGRP), substance P (SP), neurokinin A (NKA), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in healthy and inflamed human dental pulp tissue.. Six pulp samples were obtained from teeth having a clinical diagnosis of acute irreversible pulpitis. Another 12 pulp samples were obtained from premolars where extraction was indicated for orthodontic purposes. In six of these premolar teeth inflammation was induced by mechanical pulp exposure prior to sample collection. All samples were processed and 125I-labelled; neuropeptides were quantified by competition assays. ANOVA and Mann-Whitney's (post hoc) tests were used to establish statistically significant differences between the groups.. Expression of five neuropeptides was found in all human pulp samples. Statistical analysis revealed a significantly higher (P < 0.05) expression of CGRP, SP, NKA and NPY in both inflammatory conditions compared with healthy pulp control values. VIP expression remained stable during the inflammatory conditions.. Expression of CGRP, SP and NKA released from C-fibres and NPY released from sympathetic fibres is significantly higher in the inflamed human pulp compared with healthy pulp. Expression of VIP released from parasympathetic fibres is not increased during the inflammatory conditions of human dental pulp.

Topics: Adult; Calcitonin Gene-Related Peptide; Dental Pulp; Dental Pulp Exposure; Humans; Neurokinin A; Neuropeptide Y; Neuropeptides; Pulpitis; Substance P; Vasoactive Intestinal Peptide

The role of sympathetic nerves in bone physiology is largely unknown. Recent studies have shown a correlation between sympathectomy and bone remodeling. The present experiments were aimed to study the effects of unilateral sympathectomy on bilateral experimentally induced pulpitis and periapical lesions in the rat maxilla and mandible. Adult male Sprague-Dawley rats were used. Experimental rats (n=11) had the right superior cervical ganglion surgically removed (SCGx) and control rats (n=5) had sham surgery. Pulpal inflammation and periapical bone lesions in the maxilla and mandible were created 14 days later in both experimental and control rats by exposing the dental pulp in the first and second molars and leaving them open to the oral microflora. The rats were perfused 20 days thereafter and the jaws processed for immunohistochemistry with neuropeptide Y (NPY) and ED1 as primary antibodies. Sympathectomy resulted in an almost complete loss of NPY-immunoreactive (IR) fibers in the right SCGx jaws. In the non-sympathectomized (non-SCGx) left side and in the control rats, sprouting of NPY-IR fiber was observed in the inflamed pulp tissue adjacent to reparative dentin formation and in the apical periodontal ligament of the partially necrotic first molars. Significantly more ED1-IR osteoclasts were found in the resorptive lacunae lining the periphery of the periapical lesions on the SCGx side compared with the non-SCGx side (P<0.04) and the controls (P<0.03). The size of the periapical lesions were larger on the SCGx side compared with the non-SCGx side (P<0.03) in the mandible, but not in the maxilla. We conclude that inflammation causes sprouting of NPY-IR nerve fibers and that unilateral removal of the SCG increases both the area of the periapical lesions and the number of osteoclasts in the inflamed region.

Topics: Animals; Antibodies, Monoclonal; Cell Count; Immunohistochemistry; Inflammation; Male; Mandible; Maxilla; Neuropeptide Y; Osteoclasts; Pulpitis; Rats; Rats, Sprague-Dawley; Superior Cervical Ganglion; Sympathectomy; Sympathetic Nervous System

The aims of this study were to evaluate the effect of inferior alveolar nerve (IAN) axotomy on periodontal (PDL) and pulpal blood flow incident to experimental tooth movement and to investigate whether nerve fiber regeneration coincides with blood flow changes. The first right mandibular molar was moved mesially for 3, 7, and 14 days after ipsilateral IAN axotomy in 29 rats. Four rats served as unoperated controls. At the end of each experimental period fluorescent microspheres (FM) were injected into the left ventricle and thereafter counted in serial sections in the PDL and pulp of the right and left first mandibular molars. The number of FM per tissue volume was taken as a measure of blood flow. Re-innervation of nerve fibers was mapped immunohistochemically 7, 14, and 21 days after IAN axotomy in 9 rats that had no orthodontic appliance. The statistical analysis showed no significant differences in the number of FM/mm3 PDL between the denervated and the contralateral side at 3 and 7 days. At 14 days the PDL on the denervated side showed a significant increase in the number of FM/mm3, coinciding with the initial periodontal nerve fiber re-innervation. In the pulp no significant differences were found between the denervated and the contralateral, innervated side in any experimental period. It can be concluded that IAN axotomy postpones an increase in periodontal blood flow until a sensory tissue re-innervation is established, thus indicating that neurogenic mechanisms play an important role in the development of the inflammatory reaction induced by experimental tooth movement.

Topics: Animals; Axotomy; Calcitonin Gene-Related Peptide; Dental Pulp; Fluorescent Dyes; Follow-Up Studies; Immunohistochemistry; Male; Mandibular Nerve; Microspheres; Molar; Nerve Fibers; Nerve Regeneration; Neuropeptide Y; Odontoblasts; Periodontal Ligament; Periodontitis; Pulpitis; Rats; Rats, Inbred Strains; Rats, Wistar; Regional Blood Flow; Tooth Movement Techniques; Tooth Root