Clinical Review

By Dr Leo Tjaderhane, DDS, PhD, Assistant Professor, Department of Endodontics, Faculty of

Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, M5G 1G6, Canada.
Email: leo.tjaderhane@utoronto.ca

The Mechanism Of Pulpal Wound

Healing
Editor’s Note: reorganization, dentine bridge formation and pulpal healing. Some
of the materials that have been used in experimental or even clinical
This manuscript is based on an invited lecture settings are listed in Table I . From these materials, practically all -
presented at the 10th Biennial Congress of the with the exception of Teflon ( I , 2) have been able to, more or
~

European Society of Endodontology, Munich, less successfully, induce a hard tissue barrier between the exposure
Germany, 4-6 October 200 I. site and the pulp tissue

Table I: Some of the materials that have been used in

Abstract pulp capping experiments.

The favourable response of exposed pulp tissue Amalgam Dentine, native

against a variety of materials used for pulp capping in a-tricalcium phosphate Gelatin
experimental conditions, as observed by hard tissue Bioglass Glass ionomer cement
(reparative dentine) formation, demonstrates an Ca-p-glycerophosphate Hydroxyapatite
intrinsic capacity of pulp tissue for healing. However, Ca-eugenol cement Mineral Trioxide Aggregate (MTA)
in the clinical situation, in which a pulpal exposure is Ca(OH), Plasma fibronectin
Calcium phosphate (CP) Predentin
usually accompanied by a long-term external
4CP-cement Resin composites
irritation with the subsequent long-term Ceramic dentin Silicate cement
inflammatory response t o that irritation, the outcome Collagen (lyophilized) Teflon
of pulp capping procedures is not as predictable. Dentine matrix Zn(PO), cement
While some of the factors related to the defensive
reactions and healing after pulp exposure and capping
Even though the elimination of bacteria from the exposure site
procedures are well understood, the mechanisms and
and providing a bacteria-tight seal between the pulp tissue and oral
importance of others remain less well-known. cavity may be prerequisites for long-term success in the treatment
Understandingthe mechanisms regulating the spread of pulp exposures (3) these factors still do not guarantee perfect
of inflammation and necrosis in pulp tissue, and the healing in each and every case. For example, the pulp inflammation
factors regulating healing after closure of the wound, may have proceeded too far by an extensive and prolonged bac-
would facilitate the development of new and better terial irritation under a carious lesion to allow healing by elimination
of the noxious stimulus alone. Therefore, the ideal biological
treatment procedures with more predictable
treatment of an exposed pulp would include the medication -
outcomes. In this review, some of the aspects preferably delivered locally in the pulp capping material -that would
considered t o be important in pulpal wound healing help the pulp tissue to heal after the capping and closure of the
are discussed. exposure site (4). To find the ideal medication, it would be beneficial
to know and understandthe processes that occur in the pulp tissue
after the exposure and during the healing.
Introduction
For decades, dentists have tested a wide variety of treatment Table 2: The sequence of some of the variables
procedures in an attempt to retain pulp vitality after pulp exposure used in evaluation of the success and failure
by either caries, trauma or tooth preparation. The reasons may of pulp wound healing.
have varied from a real desire to retain pulp vitality, to the desperate
attempts to avoid a difficult root canal treatment. Whatever the I Absence or elimination of bacteria
reasons have been, the unpredictable results in the clinical setting 2 Initial inflammatory reaction, possibly local necrosis
have driven researchers and clinicians to try different methods and 3 Differentiation of replacement odontoblasts
materials, representing a variety of biological or practical pre- 4 Dentine bridge formation
sumptions in order to achieve the best possible, and even more - initially, reparative dentine formation

importantly, the most predictable results. - later, preferably reactionary dentine formation

The ability of the dentine-pulp complex to form hard tissue 5 Disappearance of inflammation
against a variety of materials indicates an inherent capacity for cell

68 AUSTRALIAN ENDODONTICJOURNAL VOLUME 28 No. 2 AUGUST 2002

 In pulp capping, determination of success and failure is subjective
and still a matter of controversy Table 2 lists some of the variables
that have been commonly used in studies to indicate successful pulp
wound healing It has to be stressed, however, that there is no
universal agreement as to what are the signs of true pulp wound
healing These parameters may also vary between studies, depend-
ing on the material, study protocol, follow-up time, methods of
analysis etc For example, a limit for dentine formation could be
added to the list, in that case, continuous pulp and root canal
obliteration would be a sign of uncontrolled hard tissue formation

hgure l The expression offibronectin during pulp wound healing (reproduced from Yoshiba et a/ l996, reprinted with permission from the Journalof
Dental Research)
(A) The expression of fibronectin in healthy mature human dentine-pulp border; as demonstrated with the rrnmunofluorescence technique The
fibronectin fibres are seen as bright white bands or areas at the predentine (Pd) between and under odontoblast cell layer (Od) and in the underlying
pulp tissue
(6) One week after the pulp capping, fibronectin is observed as an intensively staining layer between the necrotic layer under the capping material and
the underlying pulp tissue At this time point, the pulp cells still mostly express the fibroblast-type morphology
(C-D) After two week;, a fibronectin-containing layer ofirregular matrix (IM) between the necrotic layer and the pulp tissue is evident (C) Also,
fibronectin is present between the elongated cells located immediately under the lM (the arrow showing the fibronectin-positive fibres) (C) Toluidine
blue-staining demonstrates the odontoblast-like nature of the cells observed in connection with lM (D)
(ELF) Four weeks after the pulp capping, fibronectin-negative hard tissue formation resembling tubular dentine (TO) can be seen under the fibronectin-
negative irregular matrix (IM) (€1 hbronectin is also observed at the newly formed predentine layer between mineralised tubular dentine and well-
organised replacement odontoblast layer (Od) (F Toluidine blue-staining) The fibronectin-staining pattern after only four week; bean great similarity to
that observed in healthy tissue (A)

AUSTMLIAN ENDODONTICJOURNALVOLUME 28 No. 2 AUGUST 2002 69

 Table 3: The neurogenic and other factors regulating the inflammatory reactions, mainly blood vessel dilatation, but
also other defensive reactions in the dentine-pulp complex. The abbreviation for blood vessels (BV) has been typed
with bold to demonstrate how many factors affect the pulp vasculature during the inflammation and healing.
(Modified from Byers et al 1999). Abbreviations: S P substance P, NGF nerve growth factor, CGRP calcitonin-gene
related peptide, ACH: acetylcholine, VIP vasoactive intestinal peptide, PHI: peptide histidine isoleucine,
NE: norepinephrine, ET: endothelin, SOM: somatostatin, NKA: neurokinin, NF nerve fibres, O B odontoblasts,
F B fibroblasts, BV: blood vessels.

Action Agents Sources Initiating Events Sites of Action

Dilatation Se NGF, Sensory NF Local blood and tissue BV, symp. NF

CGRP pressure; noxious stim.
ACH, Vle PHI Parasymp. NF Autonomic reflexes Periodontal (pulpal?)BV
Constriction NE, NPY Sympathetic NF Symp. activity BV, sensory NF
ET Endothelium Vascular tone BV, sensory NF
SOM Sensory NF ?
Relaxation Nitric oxide Endoth., OB Vascular tone BV

DF outflow CGRe S t Sensory NF Hydrodynamic forces BV

NKA Local tissue pressure
DF influx NE Sympathetic NF Local tissue pressure BV

Dentinogenesis CGRP Sensory NF Hydrodynamic stim. OB

Pulp cell function NGF FB, Schwann cells Pulp cell activity-injury OB, FB, dendr. cells, BV
Sensory nerve CGRe NGF FB, dendritic cells Hydrodynamic stim. NF, BV, OB, FB,
function-location Schwann cells

and therefore a failure. Naturally, histological evaluation can usually
only be applied to experimental animal studies. In human studies,
with true clinical stituations (that is, with patients with pulp ex-
posures due to caries or trauma), the absence of symptoms and of
radiographic evidence of periapical lesions together with preserved
vitality of the pulp are the reasonable parameters that can be
studied, and histological evaluation is usually not possible.
The aim of this review is to look at some of the mechanisms
that are involved in pulpal wound healing. The paper will cover
the current knowledge of serveral aspects that participate in pulpal
wound healing, although it is not possible to cover any of them in
great detail. Instead, referencesto some of the cornerstone studies
in the field, as well as to recent review articles with more limited
scope, are given for more detailed information.
fibronectin, tenascin and growth factors, promote odontoblast
polarization and differentiation (reviewed in 4-6).The components
of basement membrane act as ligans for cell adhesion and the
growth factors, such as TGF-P I and possibly other members of the
TGF-P superfamily, regulate the differentiation of the odontoblasts
and the extracellular matrix production in the initial events of tooth
formation (4).
In pulpal wound healing, the necrotic layer may mimic at least
some of the actions of basement membrane and serve as an
attachment surface for components that induce odontoblast-likecell
differentiation or attachment (7, 8). This presumption is supported
by the experiments demonstrating that an inert pulp capping
material (Teflon) only induces soft tissue re-organization without

The Role Of The Necrotic Layer

In Pulpal Wound Healing Local inflammation Resistance J.

A layer of necrotic tissue is practically always produced at the

surface of pulpal wounds, as is also the case with other wounds. -accumulation of meta-
bolic waste products necrosis
This necrotic layer has sometimes been seen as a detrimental
side effect, and the suitability of calcium hydroxide Ca(OH),, for
example, for pulp capping has occasionally been questioned Filtration
because of the necrotic layer it causes due to the high pH. How- necrosis
Blood Row6
ever, the necrotic layer may actually be an important factor in Oedema
inducing the reparative dentine formation under the exposure site.
After the pulp exposure, healing with a hard tissue or reparative Swelling
:low compliance
dentine formation requires some kind of a surface for the attach- environment
I I

ment of the newly differentiated odontoblasts or odontoblast-like

cells. During the differentiation of primary odontoblasts, the base-
ment membrane between the differentiating ameloblasts and
odontoblasts serves as a structural meshwork that acts as a foothold
for cell immobilization. Basement membrane components such as
Figure 2 Localized inflammatory lesions are caused in the pulp by caries
and restorative procedures, while the neighbouring pulp tissue initially
remains intact At the site of inflammation, inflammatory mediaton are
released, leading to vasodilatation and decreased flow resistance See
text for details

70 AUSTRALIAN ENDODONTIC JOURNALVOLUME 28 No. 2 AUGUST 2002

 Arteriole
n after the exposure. As the healing process in the pulp exposure may
I
BI
+ b
n
.
IBI
..
U especially in the pulp horns ( I I , 12). In young teeth with their rapid
Figure 3: The schematic presentation of the pulpal vascular structures
that may regulate the pulpal blood flow during inflammation (based on
the studies by Takahashi I990 ( I 4), Takahash/et ol I996 ( / 6 ) ,using
a vascular resin cast method).
A) U-loop, that may be used to redirect the blood flow away from the
area of inflammation in order to decrease the interstitial tissue pressure.
6) Arteriovenous anastomosis (AVA), providing a shunt that can be used
to redirect the blood flow may from the inflamed area. In normal
conditions, AVAs are closed, but they may open if the venular pressure
exceeds I 9 mmHg ( I 6).
C) Constriction in the branching of the arteriole supplying the dental
pulp. The vessel walls at the branch point are composed ofwell-
developed smooth muscle, providing the branch with the structure
capable of closing or restricting the diameter of the branch (16).
hard tissue formation ( I , 2). It would also explain the good results
in the experiments and clinical work obtained with Ca(OH), in spite
of its caustic effects - or maybe at least partially because of it.
Based on the studies above, it is reasonable to assume that active
Components are needed for proper replacement-odontoblast cell-
differentation and dentine formation. A number of components that
are present in the basement membrane during the primary
odontoblast differentiation have also been suggested t o be
important in replacement-odontoblastdifferentiation and reparative
dentine formation. The role of several growth factors has been
recently discussed in an excellent review by Tziafas et al (4), and
therefore they will not be discussed here any further. The role of
other components has not been studied to that extent, with the
exception of fibronectin.
Fibronedin is one of the factors that has been suggested to
participate in the preodontoblast polarization and their terminal
differentiation, and it has been brought up as one of the key
candidates in the replacement-odontoblast differentiation (8, 9).
Yoshiba and co-workers (9)studied the expression of fibronectin
in experimental Ca(OH), pulp capping in human teeth. The study
indicates that fibronectin associated with the initially formed calcified
layer may participate in the differentiation and organization of the
replacement odontoblasts after pulp capping (9)(see Fig. I). Within
28 days after the pulp capping, the reparative dentine with some
tubular structure was already formed, and the histological structure
of the dentine-pulp border bore a great resemblance to the intact
tissue (9) (Fig. I).
It has to be noted, however, that even the results of this study
must be interpreted wirh certain caution in relation to the real
clinical situation. In this study, the pulp exposures were done to
AUSTRALIAN ENDODONTIC JOURNALVOLUME 28 No 2 AUGUST 2002
young healthy teeth, and no infection was present either before or
be, and most likely is, greatly affected and possibly compromised by
the inflammatory readions in the pulp tissue, it is possible that the
sequence is not similar with carious exposures. Also, it is reason-
able to assume that fibronectin alone is not responsible for these
changes in the pulpal wound area, but most likely a large group of
components need to act together in a highly regulated manner to
obtain the good results observed in this study.
Pulp Vasculature
Arterioles with a diameter of 0. I mm or less enter the pulp
through the apical foramen, and smaller vessels may enter the pulp
through lateral canals. In the root canal the arterioles give off
branches, which form a capillary plexus under the odontoblast cell
layer. In the pulp chamber, the arterioles branch to form a dense
subodontoblastic terminal capillary network ( I 0). Capillary blood
flow in the coronal pulp is almost twice that of the radicular pulp,
phase of dentinogenesis, capillaries may enter the odontoblast layer
to ensure the nutrition of the active cells ( 10).
The post-capillary venules continue to form larger venules,
which may be twice as large as the arterioles. The venules have
extremely thin walls, which is thought to facilitate the fluid move-
ments in and out of the vessels ( I 3).
The pulp vascular system is responsible for the nutrition and
oxygen supply for the dentine-pulp complex cells, as well as for
the elimination of noxious substances and heat produced by, for
example, tooth preparation. Therefore, it is understandable that
vascular reactions are of primary importance in the regulation of
pulp wound healing. In the following discussion we will take a closer
look at what happens in the pulp tissue during external irritation,
including pulp exposure and the events before the exposure.
The main events in the pulp vascular reactions to an external
stimulus are outlined in Figure 2. Initially, local irritation, whether
it is chemical, mechanical or thermal in nature, induces a local
inflammatory reaction, which is characterized by the dilation of the
vessels and decrease in the blood flow resistance. They, in turn,
cause an increase in intravascular pressure and blood flow in the
capillaries, leading to filtration of serum proteins and fluid into the
tissue. In addition, immunological defensive cells such as leukocytes
extravasate into the pulp tissue at the site of inflammatory response
( I 4). The increase in vascular permeability can be observed very
soon after the cavity preparation (within four hours), mainly on
the pulpal side of the capillary network under the odontoblast
layer ( 14).
The vascular reactions aim to provide the inflammatory cells to
the area, as well as to ensure that the bacterial toxins and metabolic
waste products are eliminated from the area. However, if the
external irritation exceeds the certain threshold level (for example,
there is a continuous noxious bacterial stimulus to the pulp from a
carious lesion or leaking restoration), it is possible that the reaction
is not limited to a restricted area. Because of the protein and fluid
fittration, and cell extravasation, the tissue becomes oedematous
and tissue pressure increases. In practically all other tissues, this
would lead to swelling. Due to the surrounding dentine and enamel
creating a low compliance environment, thereby preventing pulp
tissue from swelling, the tissue pressure may increase to the extent
that it exceeds the venular pressure, causingthe compression of the
venules. This is followed by increased flow resistance and con-
comitant decrease in blood flow, because the venous drainage is
impeded. The slower blood flow causes aggregation of blood cells
71

Fgure 4 Schematic presentation of the relationship between sensory
nerves and odontoblasts in rat dentine pulp (adapted from transmission
electron microscope images in lkubi et a/ l996) Wheat germ aglutinin-
horseradish peroxidase (WGA-HRP) was injected into rat trigeminal
ganglion, and the transportation of the label was observed in the
dentine-pulp complex (Ikubi et a/ l996) 00 odontoblast, NF nerve
fibre. OP odontoblast process, DET dentinal tubule
A) WGA-HRF reaction products were observed in the nerve fibres
(arrowhead) between the odontoblast cell bodies in the odontoblast cell
layer Also, label was detected in the extracellular space between the
odontoblasts and nerve axons (arrows), demonstrating secretion or
passive transportation of the labeled material into the extracellular
space
5) The vesicles containing WGA-HRP label were observed in the nerve
fibres (arrowheads), as well as in the odontoblast processes (arrow) in
dentine, indicating that nerve fibre-transported material may be
transferred into odontoblast processes
and elevation of blood viscosity, which further reduces blood flow.
The following local hypoxia, increase in metabolic waste products
and carbon dioxide, and decrease in pH lead to vasodilatation in the
adjacent pulp tissue vasculature, thus causing the spreading of
inflammation (Fig. 2) ( I 5).
As can be seen in Figure 2, an inflammatory reaction in pulp
tissue may lead to a vicious circle. If this reaction continues
uncontrolled, or (as is the case in most clinical situations) if the local
irritants (such as bacteria in the caries) are not removed, this vicious
circle may lead to local necrosis and spread further, finally resulting
in total necrosis of the pulp tissue (Fig. 2). Therefore, the total
necrosis of the pulp represents a gradual accumulation and spread
of local necrosis.
To avoid the total necrosis, there have to be measures to limit
the pulp necrosis to an area that is reasonable for the defensive
measures needed against the noxious stimulus. There is plenty
of histological evidence showing local, well-defined areas of
inflammation under caries or cavity restoration, with the adjacent
pulp tissue being completely heatthy. Pulp tissue and especially pulp
vasculature have several means of controlling the spread of the
inflammatory reaction. The tissue pressure may push the macro-
molecules into the venules in the healthy site ( I 5). That would
decrease the resistance in venules, thus improving the blood flow,
oxygen supply, and removal of metabolic waste products and other
noxious substances from the site of inflammation. In addition, the
blood vessels may locally regulate the blood flow at the site of
inflammation. Takahashi and his group (e.g. 14, 16) have success-
fully used the resin cast method to demonstrate several vascular
structures that may be used to locally control the blood flow in the
pulp. These structures include arterial U-loops and arteriovenous
anastomoses (AVAs), which may redirect some of the arterial blood
flow away from the inflamed area; and constriction sites in the
72
arteriole branching, which may decrease the blood flow into the
arterioles that would lead into inflamed area (Fig. 3). These vascular
structures may be used to redirect and control the blood flow in
order to ease the tissue pressure in the inflamed area to the level
that will allow sufficient function of the vessel system in and around
the local inflammatory area.
The Role Of Nerves In The Regulation
Of Pulp Inflammation
Dental pulp is extremely richly innervated. The nerve fibres
enter the pulp along with the blood vessels, forming a structure
frequently called a neurovascular bundle. In pulp, they follow the
arterioles. In the coronal portion of the pulp, below the odontoblast
layer there is an extensive plexus of nerve fibres, called the sub-
odontoblastic plexus of Raschkow, and the nerves also enter the
dentinal tubules especially in the pulp horn area ( I 0).
There are both sensory afferent and sympathetic, myelinated
and unmyelinated nerves in the pulp. Most of the myelinated fibres
are A-delta fibres, while C-fibres form the majority of unmyelinated
fibres. A-delta fibre terminals are mainly located close to dentine-
pulp interface, where they usually also lose their myelin sheath, and
they are responsible for sharp, pricking pain sensation. C-fibres,
sensing dull pain, are more likely distributed through the pulp ( I 3).
There are also some vibration-sensitiveA-beta mechanoreceptors
( I 7).
There is an increasing body of evidence that, in addition to the
transmission of sensory information, pulpal nerves participate in the
regulation of defensive reactions in the dentine-pulp complex. In
addition to the specific nociceptive fibres, there are many A-delta
and C-fibres that belong to a so-called polymodal receptor system.
These receptors have several features that are not usually
connected to nerve fibres. In pulp tissue, those features include at
least the regulation of inflammatory reactions, vasodilatation,
dentinal fluid outflow and pulp cell function ( 17). Indeed, the very
recent study by Rodd and Boissonade (18) indicates that the
primary function of the pulpal nerve systems may be the regulation
of the dentine-pulp complex defensive reactions, and the function
as a sensory organ would be less predictable - at least at the level
of actual subjective pain sensation ( I 8).
During the initial inflammatory reaction, as well as during the
spreading of the inflammation, endogenous inflammatory mediators
such as bradykinin, prostaglandins, histamine and interleukin- I
(IL- I ) cause vasodilatation and vascular leakage directly via vascular
receptors (reviewed in 19).They may also affect indirectly by stimu-
lation of afferent nerve endings, the very same nerve endings that
are responsible for transmission of pain ( I 9). The sensory nerves,
even if originally not involved in inflammatory reaction, may thus
become involved.
However, the external stimulus on the tooth alone causes a
release of neuropeptides, such as substance P (SP) and calcitonin
gene-related peptide (CGRP) from afferent nerves. These neuro-
peptides actually initiate pro-inflammatory vascular reaction causing
vasodilatation and the subsequent reactions as described in Figure
I , even without the effect from the endogenous inflammatory
mediators ( I 7, 19). In addition, sympathetic and parasympathetic
nerve fibres may participate by releasing substances (see Table 3),
that may either directly or indirectly participate in the regulation of
vascular reactions in pulp inflammation ( I 7).
Table 3 summarizes some of the known sources, targets and
actions of neuropeptides and other factors that participate in the
different aspects of defensive reactions in the dentine-pulp complex,
includingthose involved in pulp wound healing after the capping of
AUSTRALIAN ENDODONTICJOURNALVOLUME 28 No. 2 AUGUST 2002
an exposure. For detailed information on this fascinating and concluded that the neurogenic factors may actually participate in
increasingly growing heterogenous group of active agents in pulp the regulation of replacement-odontoblast differentiation and
tissue, there are excellent reviews available by Olgart ( I 9) and organisation (26).
Byers and Narhi ( I 7). However, several studies show that under reparative dentine,
However, there is one particular study that demonstrates the the sensory nerve fibre density is lower than under healthy dentine
importance of an intact sensory nerve system to the defensive (e.g. 24, 26, 28). It has been suggested that under reparative
reactions in pulp exposures and deserves to be discussed here in dentine the pulp inflammatory reactions may be absent or less
more detail. Byers and Taylor (20) studied the effect of denervation intense than under normal tubular dentine, and the reduced
on the pulp response to the exposure, performing sensory permeability of reparative dentine to noxious stimuli has been
denervation, (cutting the inferior alveolar nerve) on one side of rat thought to be responsible for that (4). However, part of the effect
mandibles, the other side serving as a healthy control. The pulp may be caused by the absence or reduced number of nerve
exposure of the mandibular molars performed some time after the endings, thereby providing less neurogenic pro-inflammatory
denervation, caused a rapidly progressing necrosis in exposed factors in that area.
molars compared with the respective tooth in the same animal on
the other side of the jaw. In the control teeth, an intense sprouting Conclusions
of CGRP-positive nerves was observed, demonstrating an intensive
nerve system response to the exposure and infection (20). In spite of intensive research, all the mechanisms involved in
pulpal wound healing have not been revealed yet. The prerequisite
of elimination of bacteria at the exposure site, and prevention of
The Role Of Sensory Nerves In
bacterial reappearance has gained general acceptance (3), but the
Odontoblast Function And Replacement control of the extension of inflammatory reactions,the mechanisms
Odontoblast Differentiation of replacement-odontoblast differentiation and function, and the
elimination of inflammatory reactions after initial repair processes,
Another interesting, yet currently not well understood aspect is
remain to be clarified. Exact and thorough knowledge of these
the role of sensory nerves in regulation of primary and replace-
mechanisms would facilitate the development of better and more
ment-odontoblast function. The innervation of the odontoblast
predictable treatment modalities in cases with pulp exposure and
layer, predentine and some of the dentinal tubules (at least from
partial inflammation (reversible pulpitis). New methods, such as
I00 to 200 pn from the tubular orifice) has been known about for
DNA microarray that allows comparison of the expression of
a long time ( I 7). It has been believed that the purpose of these
thousands of genes simultaneously in healthy and diseased pulp
outreaching nerve fibres is to respond to dentinal fluid movements,
tissue, may provide new and interesting pathways that will lead to
and to transmit pain sensation in dentine sensitivity (the
discoveries of new measures in the pulp treatment, with their
hydrodynamictheory originally suggested by Brannstrom (2 I )). The
biological presumption being based on observed differences in the
hydrodynamic theory would indicate that dentine sensitivity would
key gene expression profiles in healthy and diseased pulp tissues.
be caused by the movement of dentinal fluid and odontoblast
processes in the dentinal tubules causing mechanical strain to the
nerve fibres, which would be registered as pain. The possibility of References
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The Effect Of Bacterial Endotoxin On The Early Tensile Strength Of Healing
Surgical Wounds
Nitzan D., Pitaru S., Brash T , Teicher 5. / hdod 2002;
Metzger Z.,
28: 30-3.
Wound healing in the oral cavty occurs in a bacteria-rich
environment, which may affect its outcome because bacterial
contarnination has previously been show to interfere with the
normal progress of wound healing. Furthermore, it takes place
where forces are frequently applied to the healing tissue. The
present study was designed to study the potential of bacterial endo-
toxin contamination of healing wounds to inhibit their strength
development and to explore the potential of dexamethasone to
reverse this inhibition.
Collagen membranes soaked with 0.01 pg of bacterial endo-
toxin were inserted into surgical skin wounds, and their effect was
studied. Tensile strength of healing surgical wounds, which gradually
develops during the fibroblastic and remodelling stages, takes
several weeks to reach its peak. It is in its early development that
the wound is most sensitive to mechanical disruption. Because day
74
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6 is a common clinical time of suture removal, wound strength was
measured in the present study on day 6 and a few days later on day
I0 of healing. Membranes with no endotoxin served as controls.
Endotoxin inhibited the early development of tensile strength in
6 days resulting in a reduction of wound strength by 38%, whereas
the collagen membrane alone had no effect. By day I0 the wound
strength was no longer affected by the endotoxin that was initially
present. The inhibition observed might be the result of either the
direct effect of endotoxin on the fibroblasts or an indirect one by its
activation of macrophages in the wound.
Glucocorticoids have been shown to inhibit the expression of
macrophage activation both in vivo and in vitro. Dexamethasone
(0.5 mg/kg every 72 h) had a suppressive effect on the develop-
ment of tensile strength in healing non-contaminated wounds, but
not in those containing bacterial endotoxin. It is possible that this
systemic effect masked and did not allow the expression of the local
effect of the steroid on the interaction between the endotoxin-
activated macrophages and the fibroblasts.
AUSTRGLIAN ENDODONTICJOURNALVOLUME 28 No. 2 AUGUST 2002