Dental Innervation

and Its Responses to

Tooth Injury
Margaret R. Byers, PhD
Michael A. Henry, DDS, PhD
Matti V. o. Narhi, DDS, PhD
The pulpodentin complex is among the most dense-
Iy innervated tissues in the body, yet we rarely perceive
sensations from this structure unless a tooth
is injured or inflamed. We are well acquainted with
the sharp pain that is felt as soon as our teeth are
injured, and much is known about acute pain mechanisms
and dental anesthesia. However, there still are
questions about the sensory activation mechanisms
(mechanical, nociceptive, polymodal, and thermal)
and the functions of the largest A~ fibers compared
to Ao and C fibers.
Inflammatory pain mechanisms within the dental
pulp differ from acute pain and are cornplex. Evidence
is mounting that in.flammation causes molecular
changes in nerve fibers before pain is detected in
the affected tooth. This observation leads to many
questions regarding the specific role that nerve
fibers play in the dental pulp. Some of the most
intriguing are related to possible roles beyond those
associated with the perception of pain, such as contributions
to reparative processes involved in the
response to injury. What is the relationship of nerve
fibers to the other cell types within the dental pulp
and how do these relationships change following
different insults? What are the specific genes, proteins,
and receptors that are selectively activated by
the dental innervation for each condition?
This chapter highlights the advances in the
understanding of dental innervation and its injury
responses, first from general, anatomical, and neurocytochemical
perspectives in animal and human
research and then concerning the basic physiology
of pulpal nociceptors, dentinal sensitivity, and injury
reactions, with emphasis on recent advances and
reviews. Some previous seminal reviews are also
helpful.":" The related topics of pulpal vasoregulation
(see chapter 6), pain mechanisms in the pulp
(see chapter 8), pharmacologic control of tooth pain
(chapter 9), and differential diagnosis of odontalgia
(see chapter 19)are covered in other chapters.
Different questions concern recent demonstrations
that odontoblasts express neural molecules.
15-20 Much current work is focused on testing
whether that gene expression reveals direct or indirect
detection of tooth stimuli by odontoblasts and/
or an ability of odontoblasts to affect neural activity.
Alternatively, odontoblast expression of neural
genes may be part of the expanding evidence that
many non-neural ceils throughout the body adapt
those genes for non-neural requirernents." Some
use of neural signal systems might be required for
odontoblast regulation of morphogenesis of the
pulp-dentin border and its mature function as a
barrier, participation in innate immunity, supervision
of dentin matrix, interactions with vasculature,
including regulation of dentinal fluid, and responses
to injury and inflammation. Conversely (or additionally),
sensory requirements of teeth may sometimes
depend on initial activity of the odontoblasts-? or
other pulp cells.23 An understanding of these issues
is key to an understanding of why teeth have such
dense innervation and why they have special pain
problems, injury reactions, and healing mechanisms.
133
Dentallnnervation and Its Responses to Tooth Injury
Neuropulpal interactions
Sensory fibers/endinqs
Dentin f1uid Terminal glia Odontoblasts
and matrix
~/
Other pulp cells:
Syrnpathetic fibers Fibroblasts
Stem cells
, 'Dendntlc cells
, Pulp axons \
: A~, AM, AOs, Cm, Ct, Cp :

sChwafn, glia r
Nerve
I
Oral agents.
Bacteria
Immune cells
Blood vessels
Endocrine and
paracrine signals
Ganglion
Inflammation
Brainstem neurons ~ Brain perception
fmmune ceüs Glia------:lfl"'"

General Aspects of Dental

Innervation
The preservation of teeth over many decades is
enhanced by healthy dentin and pulp. Nerve fibers
contribute to tooth survival by detecting dental stimuli,
triggering dental reflexes, and interacting with
other pulp cells such as odontoblasts, fibroblasts,
blood vessels, and immunocompetent cells (Fig
7-1) for protection, maintenance of healthy tooth
function, and repair. Tooth nerves can be classified
.: based on sensory perception (perceived sharp pain,
dull pain, or prepain, compared to unperceived sensory
activity), effective stimulus (mechanical, thermal,
chemical, noxious, or polymodal), or conduction
velocity (A¡3, Aó-fast, Aó-slow, and several types of C
fiber).
Many of the nerve fibers also secrete neuropeptides
into the pulp. The timing, concentration,
and location of the neuropeptides provide important
paracrine signals for other pulp cells about the
status of the tooth. In addition to regulating normal
pulpal functions, neural agents also stimulate
neurogenic inflammation and contribute to pulp and
dentin repair" They may also mimic antimicrobial
peptides." thus providing an additional function for
neuropeptides released from fibers that innervate the
dentin and pulp.
134
Fig 7-1 Neuropulpal interactions, all 01 which can affect neural activity,
are represented with different colors: sensory endings and intradental axons
plus their terminal glia, trigeminal nerve, and ganglion (red); sympathetic
libers (orange); dental pulp cells (pink); immune cells (green); blood vessels
and inllammation (blue); endocrine and paracrine signals (yellow); lactors
lrom dentin matrix, interstitial Iluid, or dentinal Iluid (purple); oral agents
such as bacterial antigens (teel). which can penetrate into dentin; and the
central nervous system and the blood-brain or blood-nerve barriers (thick
black lines). AII 01 these interactive cells and molecules can affect the sensory
endings connected with the axons that carry the inlormation lrom the tooth
through the ganglion to brainstem to brain, where perceptions 01 tooth pain
occur. Six types 01 sensory axon are listed: three types 01 A liber (Iarge, lastest
conduction [A¡3]; medium last [Aol]; small, slow, myelinated [Aos]) and three
types 01 unmyelinated e liber (mechanosensitive [Cm], thermosensitive [Ct]
and polymodal [ep]).
During different phases of injury and healinq, the
nerve fibers (and other cells) adjust their responses,
either to enhance defensive functions or to promote
inflammation and tissue repair, and then return to
the normal resting basal condition. The neuropulpal
interactions shown in Fig 7-1 occur in preterminal
and/or terminal nerve fibers within the tooth. In
addition, nerve fibers extend long distances and
have their control center (cell body) located far away
from the tooth in the trigeminal ganglion for sensory
neurons, and in the cervical sympathetic ganglia
for sympathetic fibers, with further connections to
the central nervous system. Dental neural functions
are therefore affected by events in the brainstem,
ganglion, and alve olar or sympathetic nerves as
well as in the tooth. Chemical signals about those
events are communicated back and forth within
the neurons by fast and slow axonal transport (both
anterograde [toward the cell body] and retrograde
[away from the cell body]) as well as by the very
rapidly conducted electrophysiology signals (Fig
7-2). Those transported and conducted signals affect
neural functions at peripheral and central endings as
well as regulation of neural gene expression.
The nerve fibers in pulp and dentin are
components of a large somatosensory system that
also includes innervation of the gingiva, junctional
epithelium, periodontal ligament, tongue, lips,
mastication muscles, and temporomandibular
joint4,11,12,26 (Fig 7-3). Each part of the system
General Aspects of Dental Innervation
Fig 7-2 Two main inlormation systems lor neurons
are shown: axonal transport (a) and electrophysiologically
conducted action potentials (b). For axonal transport,
specilic molecules in vesicles or cytoplasm can go
in the retrograde direction lrom the endings (receptive
or central synaptic endings) to the cell body or in the
anterograde direction Irom the cell body out to the
endings. The rates 01 axonal transport vary Irom 1 to
400 mm/day lor the anterograde and lrom 50 to 100
mm/day lor the retrograde system, both 01 which are
much slower than the conducted action potentials. Local
cells, such as odontoblasts, libroblasts, dendritic cells,
blood vessels, and immune cells, modulate the activity 01
sensory receptive endings. At the central endings there
are modulatory interactions with glia, local neurons, axons
lrom higher centers, and endocrine and immune signals.
The receptive generator sites in the nerve endings detect
tissue stimuli such as mechanical, thermal, chemical, or
inllammatory signals. Their conducted action potentials
usually travel Irom periphery to central endings, where
they trigger synaptic communication with central neurons.
The signals in some cases I"), such as axon rellex, travel in
the opposite direction out to the peripheral endings, where
they stimulate the secretion 01 neuropeptides and other
neural agents into the pulp. CNS, central nervous system.