The role of the endogenous opioid system in modulating orthodontic-induced neurogenic inflammation of the dental pulp: A comprehensive review of the literature

Background: Orthodontic forces may lead to neurogenic inflammation in the dental pulp by triggering the release of somatosensory neuropeptides such as Substance P (SP), Calcitonin gene-related peptide (CGRP) and Neurokinin A (NKA). In the vast majority of patients, acute symptoms are not triggered, probably due to the control of the neurogenic inflammatory process exerted by endogenous opioid systems. Objective: This review aimed to assess the cellular and molecular mechanisms through which the endogenous opioid system modulates the orthodontic-induced neurogenic inflammation of the dental pulp and to identify potential mechanisms for endogenous control of pulp pain. Methods: A literature search was conducted in the databases Pubmed, ISI Web of Science and Scopus to find relevant studies using the keywords: “orthodontic movement,” “opioids” and “neurogenic inflammation.” Following the PRISMA and Amstar recommendations, studies were selected for the literature review. Results: After removing duplicated and irrelevant articles, and those that does not meet the inclusion criteria, 38 articles were selected and classified according to the opioid peptides analysed in relation to orthodontic movement and dental pulp. Discussion: Both peripheral and central pathways, via endogenous opioid systems such as somatostatin (SST), dynorphin, β-endorphin, methionine enkephalin, endocannabinoids and anti-inflammatory cytokines, modulate the neurogenic inflammation elicited by orthodontic movements. The bradykinin and monoaminergic systems also appear to display regulatory effects on pain response. These control mechanisms, however, may be insufficient in cases where severe orthodontic forces are applied, thus leading to asymptomatic irreversible pulpitis or necrosis. Conclusion: The opioid system regulates neurogenic pulpal inflammation and pain at the level of the central and peripheral nervous systems by releasing endogenous substances, including SST, opioid peptides, endocannabinoids and anti-inflammatory cytokines.