The effect of orthodontic forces on calcitonin gene-related peptide (CGRP) expression in the human periodontal ligament and its relationship with the human dental pulp

Abstract

Background The purpose of this study was to quantify the effect of moderate and severe orthodontic forces on Calcitonin gene-related peptide (CGRP) expression in the healthy human periodontal ligament (PDL) and its possible relationship with the human dental pulp. Material and Methods Ninety human periodontal ligament samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. Prior to extraction, teeth were divided in 3 groups of 30 samples each: I) Untreated teeth control group; II) Moderate force group: A 56 g force was applied to the premolars for 24 hours; and III) Severe force group: A 224 g force was applied to the premolars for 7 days. All periodontal ligament samples were processed and CGRP was measured by radioimmunoassay. Results Greater CGRP expression was found in the severe force group, followed by the moderate force group. The lower CGRP values were for the untreated teeth. Kruskal-Wallis test showed statistically significant differences between groups ( p <0.001). LSD post hoc tests showed statistically significant differences in CGRP expression between the untreated teeth and the severe forces group ( p <0.001). Differences between the moderate and severe force groups were statistically significant ( p <0.001). There was no statistically significant differences between the untreated teeth and the moderate forces group ( p <0.261). Conclusions CGRP expression in human periodontal ligament increases when teeth are submitted to severe orthodontic forces. This elevated expression of CGRP, which is proportional to the applied force, may affect the way the dental pulp responds to different stimuli from the orthodontic forces. Key words: Calcitonin gene-related peptide, orthodontic force, human periodontal ligament, neurogenic inflammation.

Pulp Changes Secondary to Orthodontic Forces: A Review of Literature

“…Orthodontic forces were found to be associated with increased flow of blood, reduction in pulpal volume, more inflammation, and CGRP expression. However, no increase in caries or root canal treatment incidence was reported during orthodontic treatment [11][12][13][14][15]. Hatrom et al studied the changes in pulp volume and root length of the upper anteriors requiring en masse retraction with and without piezo-orthodontics.…”

“…Caviedes-Bucheli et al assessed the CGRP levels after subjecting premolars that were planned for extraction to different intensities of orthodontic forces. They observed that levels of CGRP were proportional to the amount of force applied; the teeth subjected to greater force showed greater expression of CGRP by radioimmunoassay [ 12 ]. Mago et al evaluated the effect of orthodontic forces applied to upper premolars [ 15 ].…”

Using tissue clearing and light sheet fluorescence microscopy for the three‐dimensional analysis of sensory and sympathetic nerve endings that innervate bone and dental tissue of mice

“…In line with previous studies, some CGRP‐labeled fibers appeared to have no obvious relation to blood vessels and terminated as free fiber endings in the surrounding periodontal tissue (Byers, 1985 ; Heyeraas et al., 1993 ; Luthman et al., 1992 ; Uddman et al., 1984 ; Wakisaka et al., 1987 ). CGRP released from peptidergic C‐fibers in response to mechanical stress is immediate, increases the sensitivity of nociceptors by triggering the release of inflammatory mediators, and may lead to root resorption if the stress is sustained (Caviedes‐Bucheli et al., 2022 , 2008 ; Vandevska‐Radunovic, 1999 ). In the present study, we also found that the CGRP‐labeled free endings that innervated the periodontal ligament were organized in a “basket”‐like manner around the roots of the molar.…”

Endodontic–orthodontic interactions: a review and treatment recommendations

“…Also, studies have reported OTM resulted in increased release and concentrations of pulpal angiogenic growth factors that enhanced angiogenesis 29–32 . Furthermore, the finding of increased calcitonin gene‐related peptide (CGRP) expression in the human periodontal ligament (PDL) of teeth subjected to orthodontic forces, may affect the way the dental pulp responds to different stimuli 33 . The CGRP released from C‐fibres with OTM regulates inflammation by controlling vascular tone and blood flow, which results in the dynamic changes to the microcirculation in the PDL and pulp 34 .…”

“…[29][30][31][32] Furthermore, the finding of increased calcitonin gene-related peptide (CGRP) expression in the human periodontal ligament (PDL) of teeth subjected to orthodontic forces, may affect the way the dental pulp responds to different stimuli. 33 The CGRP released from C-fibres with OTM regulates inflammation by controlling vascular tone and blood flow, which results in the dynamic changes to the microcirculation in the PDL and pulp. 34 Such microcirculatory disturbances in the pulp can affect pulp metabolic activity, 35 subsequently impacting pulp sensibility such that electric pulp testing (EPT) is unreliable due to an increase in the response threshold, albeit reversible over time.…”