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NEURAL CONTROL OF PULPAL BLOOD FLOW L Olgart
NEURAL CONTROL OF PULPAL BLOOD FLOW L Olgart
L Olgart
Department of Physiology and Pharmacology, Division of Pharmacology, Karolinska Institute!, S171 77 Stockholm, Sweden
ABSTRACT: 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.
Key words. Blood flow, autonomic nerves, sensory nerves, dental pulp.
Introduction
emodynamic regulation in the dental pulp has several important functions. It serves to provide optimal nutrition to pulpal cells, supports the removal of
metabolites and waste products from the tissue, and
acts to maintain a blood pressure within the vascular
tree of the pulp in harmony with the pulpal tissue pressure. The remote neural control of pre- and post-capillary muscle sphincters in the pulp may not be the most
important regulatory system. There are also local factors,
including certain nerves, which serve to balance the
exchange between blood and tissue during resting conditions or to alter an inappropriate remote signal. Local
factors may also serve to satisfy specific demands
brought about by external stimuli. The physiology of
blood-tissue interactions has previously been extensively reviewed (Heyeraas, 1985, 1990). Therefore, the aim of
this article is critically to evaluate hypotheses about
mechanisms that regulate pulpal blood flow.
Parasympathetic System
Vasodilation as mediated by parasympathetic nerves is
part of a reflexogenic reaction in many organs, e.g., nasal
mucosa, salivary glands, skeletal muscles, and skin. For
example, the reflex-evoked cholinergic transmission
leading to salivary secretion also triggers vasodilation in
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70 -.
60 -
I|
50
CONTROL
ATROPINE
CHLORISONDAMINE
able indicator of cholinergic nerves, but studies to localize this enzyme have not been carried out on the pulp.
The other mediator (VIP), which co-exists with Ach in
post-ganglionic neurons, is released upon parasympathetic stimulation and is a candidate for mediation of the
non-cholinergic
(atropine-resistant)
vasodilation
observed in, e.g., the cat nasal mucosa and salivary
glands (Lundberg et al, 1981b,c). In oro-facial tissues,
VIP-immunoreactivity (IR) can thus be used as a marker
for parasympathetic post-ganglionic neurons. VlP-containing nerve fibers have been found in the dental pulp
of several species, including man (Uddman et al, 1980;
Akai and Wakisaka, 1990; Casasco et al, 1990; Luthman et
al, 1992), and intra-arterial injection of synthetic VIP in
the picomolar range causes vasodilation in the cat pulp
(Olgart et al, 1988). An interesting finding is that the
adjacent gingiva is sensitive to even lower doses of VIP.
Denervation experiments clearly demonstrate that the
VIP in the pulp of cats does not originate from sensory or
sympathetic nerves (Akai and Wakisaka, 1990; Olgart,
1990). However, the functional evidence for parasympathetic regulation of blood flow in the pulp is still the subject of controversy. Different results and opinions may be
partly due to differences in experimental design, techniques, and species differences.
In a preliminary study, long-lasting electrical stimulation of the lingual nerve in cats led to depletion of the
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7(2):159-171 (1996)
140
120
100
*-
80
10
140
Sympathetic System
The sympathetic system is involved in many vital functions, not all related to hemodynamic regulation. A
major role of the sympathetic system is the maintenance
of blood pressure. An appropriate stimulus triggers an
increase in sympathetic activity, which results in an
increase in blood pressure. This effect is generated by
vasoconstriction of arterioles in most tissues, and by
direct effects on the heart. Sympathetic vaso-constriction in the pulps and jaws is insignificant for circulatory
homeostasis, since these tissues represent a relatively
small blood volume. The sympathetic vasomotor control
of the pulp may have local importance.
There is overwhelming evidence that the pulpal
microcirculation is under the control of sympathetic
nerves. Taylor (1950), using vital microscopy, showed
that stimulation of the transsected cervical sympathetic
trunk caused a reduction of blood flow in rat incisor pulp.
This finding was later confirmed by Pohto and Scheinin
(1962), who also observed that an adrenaline solution
applied at the apical foramen of the rat incisor caused a
reduction of blood flow in the coronal pulp. Thus, constriction of vessels in and in the vicinity of the pulp caused
similar effects. The evidence that a-adrenoceptors exist
in pulpal vessels was based, in part, on the finding that
local application of noradrenaline (NA) on the exposed
pulp produced vaso-constriction (Ogilvie et al, 1966;
Ogilvie, 1967). Using histochemical and biochemical
techniques, many researchers have provided conclusive
evidence for adrenergic vasomotor innervation in the
dental pulp of several species, including man (Anneroth
and Norberg, 1968; Pohto and Antila, 1968b; Kukletova et
al, 1968; Larsson and Linde, 1971; Parker et al, 1986;
Kerezoudis et al, 1992; Luthman et al, 1992). The postganglionic fibers originate from the cervical sympathetic
ganglion, and after joining the trigeminal nerve at its
ganglion, most of them follow the course of the sensory
10
Time (min)
Figure 2. Experiment in human upper incisors showing the influence of atropine on changes in pulpal blood flow (upper panel)
and mean arterial pressure (lower panel) evoked by isometric
hand grip (IHG) followed by arterial occlusion of the upper arm
(OCCL). Results are expressed as percentage of baseline and
median values with 25-75 percentiles. Solid line is control
responses without atropine, and dashed line is after administration of atropine (0.015 mg/kg). * P < 0.05 compared with
baseline; ^r P < 0.05 compared with control (n = 7). Blood flow
was measured with laser-Doppler flowmetry (LDF). (Modified
with permission from Aars et al., 1993.)
nerves to the teeth and adjacent tissues in the cat and rat
(Matthews and Robinson, 1980; Marfurt et al, 1986;
Kerezoudis et al, 1995). In the rat, a small but significant
proportion of the sympathetic nerves follow another
route to the teeth, possibly traveling via the vessels
(Kerezoudis etal, 1995).
Detailed functional studies have shown that sympathetic vasoconstriction in the cat and dog pulp is mediated mainly by vascular receptors of the a,-type (Edwall
and Kindlova, 1971). These receptors are located postjunctionally, e.g., on the vascular smooth muscle cells.
Adrenoceptors of the a 2 -type are located both preand post-junctionally. Activation of pre-junctional
a 2 -adrenoceptors by NA results in a reduced aj-evoked
vasoconstriction, due to an auto-inhibitory control of NA
release from the sympathetic nerve endings. Post-junctional activation of a 2 -receptors usually results in a weak
161
4 Hz
16 Hz
4Hz
16 Hz
-20 -
-40 -
-60 -
-80
T T
vasoconstriction. Pulpal vessels in the dog, like periodontal vessels in the cat, are equipped with both a,and a2-adrenoceptors (Edwall et al, and Gazelius, 1988;
Kim et al, 1989; Ibricevic et al, 1991). The influence of
vasoconstrictor a2-receptors on blood flow in the dog
and the cat was shown to be smaller than that of
a,-receptors. Evidently, there are species differences,
since in the rat incisor the a2-adrenergic blocker idazoxan was shown not to influence sympathetic vasoconstriction (Fig. 3) (Kerezoudis etal, 1993a). The a-adrenoceptors seem to be distributed at both the arterioles and
the venules in the rat dental pulp (Kim et al, 1989). This
may mean that the remote sympathetic control can
selectively regulate the pre- and post-capillary sphincters in the pulp in order to adjust pressure in the intermediate capillary sections, as required by the tissue.
However, such selective regulation of regional flow has
not been demonstrated. There is no detailed description
about the distribution of adrenergic receptors in the
human teeth.
The influence of sympathetic activity on pulpal circulation in resting conditions seems to be low in both
animals and man. In anesthetized animals in a supine
position, cutting the sympathetic nerve or administering
an a-adrenoceptor antagonist does not alter blood flow
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200
CD
E 100
a.
GQ
10
8
LL
420
min
163
ARTERIAL
PRESSURE
mm Hg
100
DISAPPEARANCE
RATE
k 102min'
TIME ( 4 0 s e c )
SIGNAL
Local Modulation
2001
6.
4 hours
Figure 5. Influence of deep cavity preparation on sympathetic vasoconstrictor response in the pulp of the cat; initial response (1) and
after 4 hours (2). 1 , 2 sympathetic stimulation with 6 Hz. Pulpal
blood flow was measured with the iodide disappearance technique.
(From Forssell-Ahlberg and Edwall, 1977, with permission.)
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7(2):159-171 (1996)
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100
lOG
165
Activation
Sympathetic
Nerve
Figure 7. Schematic drawing showing proposed bidirectional
interactions between remote (sympathetic) control and local
(sensory) control of pulpal blood flow. Sympathetic vasoconstriction (a) is counteracted by local activation of sensory nerves
and release of vasodilator neuropeptides (CGRP and SP) (b).
Reflex activation (c) of sympathetic nerves and local release of
NA attenuates the release of CGRP and SP (d).
Sympathetic modulation of
local vascular reactions
Rat incisor teeth provide a special feature in that both
sympathetic vasoconstriction and sensory nerveinduced vasodilation may be studied in response to
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7(2):15<M71 (1996)
Conclusion
The remote (autonomic) neural control of pulpal blood
flow is not tonically active but is typically activated by
stress stimuli and by painful stimuli directed at almost
any part of the body. Thus, the documented effects of
sympathetic and parasympathetic nerves on pulpal
blood flow are mostly incidental and reflect a more widely spread of centrally mediated reflexes that affect much
of the body. There is no evidence for pulpal blood flow
being selectively adjusted by sympathetic or parasympathetic nerve activity to meet specific requirements of the
tissue.
Local neural control, on the other hand, operates on
a local scale. When triggered by a local stimulus (usually a painful one), a subset of intradental sensory fibers
mediates relaxation of pulpal vessels by counteracting a
myogenic or sympathetic vasoconstrictor tone. Many
other non-neural mechanisms, including endotheliumderived vasoactive principles and local tissue pressure,
also contribute to maintaining an optimal blood circulation in the normal pulp.
In the compromised pulp, the remote vasoconstrictor control is attenuated, and the delicate interplay
between local mechanisms may be put out of balance.
Blood circulation in such a pulp becomes very dependent on alterations in systemic perfusion and tissue
pressures, and this may contribute to further progress of
pulp inflammation.
Future Directions
The present knowledge about regulation of pulpal blood
flow is based mainly on results obtained in anesthetized
animals. We need critically to confirm and extend this
knowledge by studying the pulp in conscious humans.
Methods are available, such as non-invasive laserDoppler flowmetry for blood flow recording, and electrophysiological techniques for recording of nerve functions. Novel biochemical techniques should also be
applied on pulps of extracted human teeth and teeth in
situ for the tracing of alterations in the expression of
mediators of neurovascular reactions. Perhaps some of
these functional and biochemical parameters obtained
in humans will show the existence of even more complex
interactions among the many regulatory systems in the
pulp than we thought.
Circulatory control should also be further studied in
pulps with early signs of inflammation in both animals
and man. Such studies have been hampered by difficul-
167
Acknowledgments
This review is based upon valuable collaboration with many colleagues
and students, to whom I am greatly indebted. This work was supported
by Swedish MRC Grant 00816 and Karolinska Institutet.
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