The Effects of Orthodontic Mechanics on the

Dental Pulp
Masaru Yamaguchi and Kazutaka Kasai

Orthodontic forces are known to produce mechanical damage and inflam-

matory reactions in the periodontium, as well as cell damage, inflammatory
changes, and circulatory disturbances in dental pulp. Orthodontic forces
should produce periodontal inflammatory reactions but should not show
effects beyond mild inflammation of human dental pulp. It is known that
orthodontic forces are capable of stimulating the whole vascular system in
the dental pulp. Results of published histological data demonstrated that
the dental pulp is affected by the orthodontic forces in the form of circula-
tory vascular stasis to necrosis. Recent studies reported that there will be an
increase in expression of sensory neuropeptides, such as substance P (SP)
and calcitonin gene-related peptide, in dental pulp following orthodontic
force application in rats. The release of SP, further stimulating release of
proinflammatory cytokines such as interleukin (IL)-1␤, IL-6, and tumor ne-
crosis factor-␣ from human dental pulp fibroblasts, could implicate its role in
development of internal resorption associated with orthodontic mechanics.
This article reviews the current knowledge of the biological aspects of
dental pulp tissue changes incident to orthodontic tooth movement. (Semin
Orthod 2007;13:272-280.) © 2007 Elsevier Inc. All rights reserved.

rthodontic tooth movement is facilitated
O by remodeling changes in the periodontal
ligament (PDL) and alveolar bone in response
to the applied mechanical stimuli. A precondi-
tion for these remodeling activities, and ulti-
mately tooth displacement, is the occurrence of
an inflammatory process. Vascular and cellular
changes were the first events to be recognized
and described followed by release of a number
of inflammatory mediators, growth factors, and
neuropeptides in periodontal supporting tis-
Senior Lecturer, Department of Orthodontics, Nihon University
School of Dentistry at Matsudo, Matsudo, Japan; Professor, Depart-
ment of Orthodontics, Nihon University School of Dentistry at Mat-
sudo, Matsudo, Japan.
Address correspondence to Masaru Yamaguchi, DDS, PhD,
Department of Orthodontics, Nihon University School of Dentistry at
Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587,
Japan. Phone: ⫹81 047-360-9414; E-mail: yamaguchi.masaru@
nihon-u.ac.jp
© 2007 Elsevier Inc. All rights reserved.
1073-8746/07/1304-0$30.00/0
doi:10.1053/j.sodo.2007.08.008
sues. Their increased levels during orthodontic
tooth movement have led to the assumption that
interactions between cells producing these sub-
stances, such as nerve, immune, and endocrine
system cells, regulate the biological responses
that occur following the application of orth-
odontic forces.1
The effects of orthodontic forces on the den-
tin-pulp complex have not yet been significantly
investigated. In the permanent tooth, the hard
calcified tissue has a core of soft vascularized and
innervated tissue, the dental pulp. The innerva-
tion of dental pulp includes sensory nerve fibers,
which may also subserve dentinal fluid dynamics
and regulate pulp blood flow, providing reflexes
to preserve dental tissues and promote wound
healing.2 The main neuropeptides associated
with these functions include substance P (SP),
calcitonin gene-related peptide (CGRP), and
neurokinin A (NKA), which are abundant in the
pulp and periodontium3,4 Release of these neu-
ropeptides after stimulation of sensory nerve fi-
bers induces vasodilatation and increases vascu-

272 Seminars in Orthodontics, Vol 13, No 4 (December), 2007: pp 272-280

 Orthodontic Mechanics and Dental Pulp
lar permeability, a condition referred to as a
“neurogenic inflammation.”5-7 Therefore, a re-
cent concept is that stimulation of sensory
nerves with any kind of mechanical or physical
force may induce pulpal change such as induc-
tion of neurogenic inflammation followed by
alteration of pulpal blood flow.
Kvinnsland and coworkers have found a mild
inflammatory type response in the dental pulp
that has been subjected to orthodontic forces,8
but specific cellular responses have not been
investigated. This article reviews the current
knowledge of the biological aspects of inflamma-
tory changes in dental pulp in response to orth-
odontic tooth movement.
Pulpal Reactions
Profitt and Fields9 stated that “although pulpal
reactions to orthodontic treatment are minimal,
there is probably a modest and transient inflam-
matory response within the pulp, at least at the
beginning of treatment.”10 The latter may con-
tribute to the discomfort that patients often ex-
perience for a few days after appliances are ac-
tivated.
There are occasional reports of loss of tooth
vitality during orthodontic treatment. Usually
this is preceded by previous trauma to the tooth,
but poorly controlled orthodontic forces some-
times are the culprit. If a tooth is subjected to
heavy continuous force, a sequence of abrupt
movements occurs, as undermining resorption
allows increasingly large increments of change,
which are capable of severing the blood vessels
at their point of entry. Loss of vitality has also
been observed when incisor teeth were tipped
palatally or labially to such an extent that the
root apex, moving in the opposite direction, was
actually moved outside the envelope of the alve-
olar process. Such movements are prone to in-
duce damage to the blood vessels entering the
pulp canal.
Results of published histological data demon-
strated that the dental pulp is affected by the
orthodontic movement, showing pulp reactions
ranging from circulatory vascular stasis to necro-
sis.11-14 Butcher and Taylor observed that the
application of retraction forces caused pulp
necrosis in monkey teeth. Studies done on
humans showed that intrusive and extrusive
forces caused odontoblastic layer degeneration
273
due to circulatory disturbances in dental pulp.12,13
Anstendig and Kronman could observe disrup-
tion of the odontoblastic layer after bodily move-
ment and torque force on dog’s teeth.10 As part
of his experimental study, Turley and coworkers
traumatically intruded dog teeth followed by
orthodontic extrusion. They observed that half
of the teeth became totally necrotic while the
rest showed calcification and degeneration of
the pulp tissue.14
Neuropeptides and Inflammatory
Cytokines
The peripheral sensory nervous system contrib-
utes to the development of acute and chronic
inflammatory processes through local release of
neuropeptides. A number of different neu-
ropeptides, including SP and CGRP, are known
to be present in the nerve fibers that supply
tooth pulp and the periodontium in rats, cats,
monkeys, and humans.15-20 SP, a sensory neu-
ropeptide released by the peripheral nerve end-
ings during inflammation, is capable of modify-
ing the secretion of proinflammatory cytokines
from immunocompetent cells. SP has also been
reported to induce the secretion of interleukin
(IL)-1␤, IL-6, and tumor necrosis factor (TNF)-␣
from monocytes.21,22 Further, a change in the
morphology and distribution pattern of CGRP
and SP was observed as a result of local pulp
trauma, which may indicate its role in the in-
flammatory process associated with tissue injury
and repair.23
Caviedes-Bucheli and coworkers reported that
the expressions of SP, CGRP, and neurokinin A
(NKA) in inflamed human dental pulp tissue
were significantly higher when compared with
pulp from healthy controls.24 In addition, it was
observed that the expression of CGRP or SP, or
both, increases in dental pulp in response to
orthodontic tooth movement in rats, cats, and
humans.25-28 Norevall and coworkers suggested
that these neuropeptides might be involved in
inflammation of the dental pulp at the time of
orthodontic tooth movement.29 The laboratory
of the authors of the present article could dem-
onstrate that SP and CGRP could stimulate the
production of IL-1␤, IL-6, and TNF-␣ in human
dental pulp fibroblasts (HDPF) in vitro.30 Fur-
ther, Kojima and coworkers reported that SP
significantly stimulated the production of pros-
274 Yamaguchi and Kasai
taglandin E2 (PGE2) and the receptor activator
of NF-kappaB ligand (RANKL) by HDPF cells,
and the increase of RANKL caused by SP stimu-
lation in HDPF cells was partially mediated by
PGE2.31 Taken together, these findings along
with those of the present authors’ results suggest
that HDPF may be actively involved in the
progress of inflammation in pulp tissue during
orthodontic tooth movement.
Vasodilatation and Angiogenic Response
to Orthodontic Forces
Blood flowing through the tooth is confronted
with a unique environment. The dental pulp is
encased within a rigid, noncompliant shell and
its survival is dependent on the blood vessels that
access the interior of the tooth through the api-
cal foramen. As a consequence of these unusual
environmental constraints, changes in pulpal
blood flow or vascular tissue pressure might
bring in serious implications for the health of
the dental pulp.3,32
The role of the vascular system in tooth move-
ment incident to orthodontic force application
has been studied by several investigators.11,33-38
It was observed that even small forces of short
duration, that is, around 4 hours, may be ade-
quate to evoke cellular responses.39 Early mor-
phologic investigations speculated that orth-
odontic treatment may cause a decrease in
blood flow to the pulp.11,12 Labart and cowork-
ers demonstrated an increase in pulpal respira-
tion rate in rat incisors (1-2 times more than
controls) when subjected to orthodontic stress
for 72 hours.40 Unsterseher and coworkers37 and
Hamersky and coworkers38 observed that pulp
tissue respiration was depressed between 27%
and 33% after orthodontic force application.
McDonald and Pitt Ford reported that there
will be an initial decrease lasting approxi-
mately 32 minutes, followed by an increase
(lasting 48 hours) in pulpal blood flow after
orthodontic force application.41 Kvinnsland and
coworkers observed a substantial increase in the
pulpal blood flow in mesially tipped rat molars
for 5 days.8 Wong and coworkers also reported
that simple tipping of a tooth 2 mm buccally
resulted in an increase in the vascular supply to
pulp of that tooth.42 With the help of histologic
observations, Mostafa and coworkers reported
that orthodontic forces might produce conges-
tion as well as dilation of blood vessels along with
edema of pulpal tissue.13 It is also reported that
the induced tooth movement yielded an in-
crease in the vascular volume density, when com-
pared with the control group at 6 hours. Fur-
ther, the increase of vascular volume density
returned to similar values in the control group at
24 and 72 hours of force application.43 On the
contrary, Nixon and coworkers could observe an
increase in the number of functional pulpal ves-
sels for 14 days after orthodontic force applica-
tion.44
Angiogenesis is the formation of new capillary
structures ultimately leading to the organization
of larger structures by a process of neovascular-
ization.45 Angiogenesis is mainly found in the
developing embryo, developing or growing tis-
sue, wound healing and repair, and inflamma-
tory and pathological processes involving growth
of blood vessels. Angiogenesis is a complex pro-
cess with extracellular matrix remodeling, secre-
tion of proteolytic enzymes, endothelial cell migra-
tion and proliferation, capillary differentiation,
and anastomosis.46 Angiogenesis is regulated by
the interplay of numerous cytokines and growth
factors. Among all the proangiogenic factors,
vascular endothelial growth factor (VEGF) is
considered the most essential for the differenti-
ation of the vascular system.47 Basic fibroblast
growth factor (FGF-2) is also known to stimulate
angiogenesis in vivo and is thought to play an
important role in neovascularization of dam-
aged or traumatized tissue.48 Tran-Hung and
coworkers reported that human pulp fibroblasts
express both FGF-2 and VEGF, and suggested
that these molecules exert their angiogenic ef-
fects as soluble factors.49 The release of FGF-2
and VEGF is very rapid and corresponds well to
the pathological changes in the pulp following
injury. After pulp injury, the odontoblast pro-
genitor cell migration to the injury site may
require newly formed blood vessels. Odonto-
blast progenitor cells can be initiated by the
secretion of angiogenic growth factors by den-
tal pulp fibroblasts. Derringer and coworkers
reported that there were significantly greater
increase in number of microvessels at days 5
and 10 of culture in the pulp explants from
orthodontically treated teeth, when compared
with those from the pulps of control teeth.50
Recently, Derringer and coworkers identified
the specific angiogenic growth factors released
 Orthodontic Mechanics and Dental Pulp 275

Table 1. The Effects of Various Orthodontic Forces Dental Pulp and Various Orthodontic
on Pulpal Blood Flow Forces
Orthodontic
Force Symptoms Reference Application of an intrusive force to monkey in-
cisor teeth has been reported to cause necrosis
Intrusion Blood flow (2) (11) (12) (61) (62)
Blood flow (⫾) (64)
of the pulp tissues.11 The effects of intrusive
Extrusion Blood flow (⫾) (61) force on human teeth have also been examined
Circulatory disturbances (13) histologically.12,52 These studies reported that
Tipping Blood flow (2) (47)
Blood flow (1) (8) (48) the main pulp changes observed were vasodila-
tation and circulatory disturbances, local hem-
orrhage, and brown hemosiderin deposits from
red blood cell degradation. According to Pic-
in response to orthodontic force application ton,53 a brief intrusive force of 50 g causes an apical
to be VEGF, FGF-2, platelet-derived growth tooth displacement of approximately 40 ␮m,
factor (PDGF), and transforming growth fac- which is sufficiently large to distort blood vessels
tor (TGF)-␤.51 It is clear from the ongoing of 30 to 150 ␮m in diameter.54 Brodin and
discussion that orthodontic forces might be coworkers and Sano and coworkers reported
involved in stimulation of vasodilatation and that brief intrusive force (0.5-2.0 N) produced
angiogenesis in dental pulp tissues. a transient apical displacement of tooth result-

Figure 1. Effects of substance P (SP) on (A) interleukin (IL)-1␤, (B) IL-6, and (C) tumor necrosis factor
(TNF)-␣ production from human dental pulp fibroblasts obtained from patients with severe root resorption.
HDPF cells were incubated with or without the indicated concentrations of SP for 12 hours. Data are expressed
as the mean ⫾ SD of 5 independent cultures. The cytokines were increased by incubation with SP. Significantly
different from the corresponding control of SP: *P ⬍ 0.001. Significantly different from nonresorption (NR)
group (with SP) at each incubation dose: #P ⬍ 0.001.
276 Yamaguchi and Kasai
ing in significant reduction of pulpal blood
flow because of compressed blood vessels.55-57
Contrary to these reports, Barwick and Ramsay
reported that pulpal blood flow is not altered
during the application of a brief intrusive orth-
odontic force.58
Reitan and Vanarsdall recommended that the
extrusive force for adults should be kept be-
tween 25 to 30 g to prevent pulpal damage.59 On
the other hand, Profitt and Fields considered
that a range of 50 to 75 g force is the optimum
force magnitude for extrusion.9 Subay and co-
workers reported that the extrusive forces (75 g)
applied did not cause significant deleterious ef-
fects on the odontoblasts.60 Mostafa and coworkers
demonstrated that extrusive forces caused odonto-
blastic layer degeneration due to circulatory distur-
bances in human pulp tissue13 (Table 1).
Other types of orthodontic forces, such as
tipping and bodily movement, if applied in ex-
cess are also capable of altering pulpal respi-
ration rate and37,38 disruption of the odonto-
blastic layer13 resulting in pulpal necrosis.12
These data open up new avenues for future
research to evaluate changes in the pulpal
blood flow following application of various
orthodontic forces.
Internal Resorption
Orthodontically induced inflammatory root re-
sorption (OIIRR) is an unavoidable pathologic
consequence of orthodontic tooth movement. It
can be defined as an iatrogenic damage that
occurs, unpredictably, after orthodontic treat-
ment, whereby the resorbed apical root portion
is replaced with normal bone. OIIRR is a sterile
inflammatory process that is extremely complex
and involves various disparate components in-
cluding mechanical forces, tooth roots, bone,
cells, surrounding matrix, and certain known
biologic messengers.61 The etiology of OIIRR
following orthodontic treatment is not fully un-
derstood. Harris and coworkers reported that
the sum of the effects of patients’ sex and age,
the severity of the malocclusion and the kind of
mechanics used accounts for little of the overall
variation in OIIRR.62 In the last 10 years, inter-
estingly, it was suggested that individual suscep-
tibility,63,64 genetics,65 and systemic factors66 are
also the risk factors for OIIRR.
Orthodontic forces are known to produce
mechanical damage and inflammatory reactions
in the periodontium,35 as well as cell damage,
inflammatory changes, and circulatory distur-
bances in dental pulp.36 Kucukkeles and Okar
reported that the inner root surface of the pulp
in teeth subjected to intrusive force induced
resorption cavities.67 This report was in concor-
dance with previous studies, which reported that
the endodontically treated teeth resorb signifi-
cantly less than their contralateral controls. Re-
sults of these studies point to the fact the dental
pulp might be involved in the incidence of in-
ternal resorption following orthodontic me-
chanics.68-71 Nixon and coworkers found a force-
dependent increase in predentin width, which
corresponded to the time of peak tooth move-
ment cycle in rats.44 Stenvik and Mjor reported
that wherever degenerative changes predomi-
nated, there was an increased activity in the
odontoblast layer.12
Recently, the laboratory of the authors of the
present article reported that SP stimulated the
Figure 2. Resorption pits on dentin slice surface. Re-
sorption pits were more abundant in the group of
severe root resorption (SRR) (with SP) than in the
control group (without SP). Nonresorption (NR)
(without SP). Severe root resorption (SRR) (without
SP). Nonresorption (NR) (with SP). Severe root re-
sorption (SRR) (with SP). Resorption areas (␮m2)
were measured and statistical analysis performed on
the results. Data are expressed as the mean ⫾ SD of 5
independent cultures. Significantly different from
corresponding control (*P ⬍ 0.001). Significantly dif-
ferent from nonresorption (NR) (with SP) (#P ⬍
0.001).
 Orthodontic Mechanics and Dental Pulp
production of IL-1␤, IL-6, and TNF-␣, PGE2, and
RANKL in HDPF in vitro.30,31 Further, results
obtained from studies conducted in the labora-
tory of the other researchers indicated that SP
stimulated IL-8 from HDPF.72,73 However, very
little is known regarding the relationship be-
tween internal resorption and inflammation in
human dental pulp. Thus, the authors of the
present manuscript examined the effect of SP
on the production of IL-1␤, IL-6, TNF-␣, and on
osteoclast formation from HDPF obtained from
patients with severe internal OIIRR.74 The re-
sults demonstrated that stimulation with SP
increased the levels of IL-1␤, IL-6, TNF-␣,
PGE2, and RANKL in a time- and concentra-
tion- dependent manner. The increase was
greater in the severe root resorption (SRR)
group than in the nonresorption (NR) group.
The numbers of tartrate resistant acid phos-
phatase (TRAP)-positive multinucleate cells
and resorptive pits suggestive of osteoclasto-
genesis were significantly increased in the SRR
group, when compared with the NR group
(Figs 1 and 2). These results suggest that
HDPF cells produce a large amount of proin-
flammatory cytokines in response to SP, and
Figure 3. Schematic presentation of pulpal inflammation incident to orthodontic force.
277
may be involved in the progression of pulpal
inflammation and in the incidence of severe
root resorption during orthodontic treatment.
The process is depicted schematically in Fig 3.
Concluding Remarks and Future
Research
Orthodontic force may induce pulpal change in
the form of induction of neurogenic inflamma-
tion leading to release of neuropeptides. These
neuropeptides are involved in alteration of pul-
pal blood flow and release of proinflammatory
cytokines leading to pulpal inflammation and
hyperemia. If the force applied is excessive,
there will be abnormal pulpal respiratory rate
and altered or congested blood flow leading to
iatrogenic damage in the dental pulp. This iat-
rogenic damage can range from simple necro-
sis to even internal root resorption. As the
investigations performed are very few in this
regard, further studies are necessary to con-
firm the pulpal reactions that might occur
when mechanical force through orthodontic
appliances is used.
278 Yamaguchi and Kasai
Acknowledgment
This research was supported in part by a Nihon University
Individual Research Grant for 2005 (to M. Yamaguchi; 05-
119) and 2006 (to K. Kasai; 06-090).
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