P H Y S I O L O G Y ( O R A L BO I ROA LL OBGI O

Y L) O G Y

The Neural Mechanisms of Oral and

Facial Pain
SAMUEL W. CADDEN AND ROBERT ORCHARDSON

sufficient to provide a diagnosis. By

Abstract: Pain is a complex and variable phenomenon that can be influenced by many definition (see above), pain usually
factors. The neural pathways serving pain are not passive conduits, but are part of a signifies that something is wrong, such
dynamic system which can result in different levels of pain resulting from similar
as tissue damage or disease. However,
injuries under different circumstances. The passage of signals in these pathways may
be inhibited or enhanced at almost any level, from the peripheral sensory receptors to
although many pains have an obvious
the higher centres of the brain. This review will describe recent developments in our cause (e.g. dental caries) and can be
understanding of these mechanisms and how this knowledge may be used in alleviated by removal of that cause,
controlling pain. some pains arise where there is no
obvious tissue damage. Conversely,
Dent Update 2001; 28: 359-367 some quite severe injuries may cause
Clinical Relevance: An understanding of the neural processes responsible for pain little or no pain. A further problem from
and the factors that can modify them is important for the effective management of a clinical standpoint is that the source
orofacial pain. and site of a pain may be different – the
phenomenon of referred pain. Such
pains are usually referred between
structures of common embryological
origins. When this happens, they are
described as being segmental since

P ain may be defined as:

an unpleasant sensory or
emotional experience associated
with actual or potential tissue
damage, or described in terms of
such damage
(International Association for the Study
of Pain1). The term nociception,
although more difficult to define,
generally refers to the activation of
neural pathways by stimuli that damage
or threaten to damage the tissues
(noxious stimuli). Pain is one result of
nociception (as are some reflexes,
Samuel W. Cadden, BSc, BDS, PhD, FDS RCS
(Edin.), Senior Lecturer in Oral Biology, Unit of
Clinical Dental Sciences,The Dental School,
University of Dundee, and Robert Orchardson,
BSc, BDS, PhD, FDS RCPS (Glasg.), Senior
Lecturer in Physiology, Institute of Biomedical &
Life Sciences, Laboratory of Human Anatomy,
University of Glasgow.
changes in arousal, etc.) but the words
are not synonymous.
Much of our understanding of the
mechanisms of pain comes from studies
not of pain itself, but of nociception in
anaesthetized animals (which by
definition do not feel pain).
There are many types of orofacial
pain2 (see Table 1). Although the dentist
may view pain from the teeth and
temporomandibular region as the most
common problems with which he or she
has to deal, it is difficult to provide
precise information on the prevalence of
these and other orofacial pains because
of procedural differences in different
epidemiological studies.3 These
differences include the questions asked,
the nature, severity and duration of the
pain, and demographic factors.
Pain is an important clinical symptom
and is one of the classical components
of inflammation (dolor, calor, rubor,
tumor). Indeed, the pattern and
presentation of pain can often be
both the source and apparent location
of the sensation fall within the same
neural segment of the body. For
example, dental pains may be referred to
the ear or face – all three structures
being within the distribution of the
trigeminal nerve.
Intracranial pain disorders
Primary headache disorders (neurovascular
disorders)
Neurogenic pain disorders:

Paroxysmal neuralgias

Continuous pain disorders

Sympathetically mediated pain
Intra-oral pain disorders
Temporomandibular pain disorders
Pain arising from disorders of associated
structures (e.g. eyes, ear, nose and throat)
Pain associated with mental disorders (e.g.
psychogenic pains)
Table 1. Classifications of the origins of orofacial
pains. Based on a table published by the
American Academy for Orofacial Pain.2

Dental Update – September 2001 359

 O R A L B I O L O G Y
Thus pain is clearly not a simple
sensation whereby a stimulus of
sufficient strength will always produce a
sensation that grows in intensity with
the strength of the stimulus. Seemingly
comparable injuries or disease states
can produce different levels of pain in
different people, and even in the same
person at different times. In this review
we will consider how these differences
occur. We will concentrate on the
mechanisms associated with simple
acute pain, i.e. pain resulting from a
noxious stimulus or tissue injury. In so
doing, we will bear in mind that most
knowledge of these mechanisms derives
from studies of the limbs rather than the
orofacial region. However, there is
adequate evidence to make one believe
that mechanisms operating in the spinal
cord also apply to the trigeminal
system.4
PERIPHERAL MECHANISMS
OF PAIN
Nociceptors
As pain is a perception, not a stimulus,
the term ‘pain receptor’ is not
appropriate. Instead it is more proper to
refer to the receptors that respond to
harmful or potentially harmful (noxious)
stimuli as nociceptors. This is
particularly helpful as some stimuli can
excite nociceptors without producing
pain (e.g. temperatures around 41°C).5
From a morphological point of view,
most or all nociceptors are believed to
be free nerve endings. However, they
differ with respect to whether their
axons are myelinated (A-fibres) or
unmyelinated (C-fibres) and in their
responsiveness to particular forms of
noxious stimuli.
A-fibre Nociceptors
With occasional exceptions (e.g. the Aβ
nerves supplying tooth-pulp 6), all
myelinated nociceptors may be
categorized as Aδ fibres, i.e. the thinnest
myelinated nerves. In humans, most Aδ-
fibre nociceptors respond only to
noxious mechanical stimuli7 and are
known as A-mechanical nociceptors or
360
Damage
Damage
Skin or
mucosa
Phospholipids Kallikrein
* Platelet
Aggregation
H+
Kininogens
Arachidonic K+
Acid
Mast Bradykinin
** Serotonin
Cells
Peptides
Histamine
Prostaglandins
Leucotriens
Nociceptive Nerve Ending
Figure 1. Tissue damage produces local chemical changes which can either directly or indirectly
affect nociceptive nerves. Some chemicals can activate or sensitize the endings, depending on whether
they are in high or low concentrations respectively (purple arrows). Others can only activate (blue
arrows) or sensitize (green arrows). Note that the release of neuropeptides from the nerve ending itself
(orange arrow) contributes to this process by what amounts to a positive feedback mechanism. The
diagram also shows the sites of action of steroidal (*) and non-steroidal (**) anti-inflammatory drugs.
For clarity of presentation, not all the putative inflammatory agents are shown here (see text). Modified
from Le Bars and Willer.9
Aδ-mechano-nociceptors.7–9 The next C-fibre Nociceptors
largest group of Aδ-fibre nociceptors Most of the unmyelinated nociceptors
responds to all types of noxious stimuli are also polymodal, responding to
(mechanical, thermal, chemical) – or at strong mechanical stimuli, intense heat
least to all the types with which they or cold and various pain-producing
have been tested7 – and are usually chemicals. C-fibre polymodal
called Aδ polymodal nociceptors.7–9 nociceptors are the most numerous7 and
Other Aδ nociceptors, which respond arguably the most important9
only to cold, or to hot and chemical but nociceptors in the human body.
not mechanical noxious stimuli, have In some parts of the body, a brief
also been reported7,10 but their strong (e.g. electrical) stimulus can
importance is not yet clear. evoke two distinct painful sensations –
Dental Update – September 2001

ARACHIDONIC ACID
COX-1 COX-2
(constitutive) (inducible)
“Protective”
or “Inflammatory”
“Physiological” Prostaglandins
Prostaglandins
Gastric protection Inflammation
Haemostasis Pain
Vasodilation
Renal Function
Figure 2. Arachidonic acid may be converted
into prostaglandins by the enzymes COX-1 and
COX-2. The protective functions of prostaglandins
are produced by relatively low concentrations,
which are regulated mainly by COX-1, the
constitutive form of the enzyme. COX-2 also has a
limited constitutive role in some normal tissues, but
this isoenzyme is expressed mainly in damaged
tissue. COX-2 produces the same prostaglandins
as does COX-1, but in greater amounts. Thus,
the effects of prostaglandins in inflamed tissues
are due principally to their increased
concentrations rather than to the actual
prostaglandins present.
first (fast) and second (slow) pain – due
to the very different speeds of impulse
propagation in Aδ- and C-fibres
respectively. However, these two
components cannot easily be
distinguished in the orofacial region
because of the short conduction
distances to the brain. Although
probably a simplification, it is often said
that first and second pains correspond
to the sharp and burning pains that
occur successively during and after an
injury.
Chemical Changes in Damaged
Tissues
Damaged tissues release a cocktail of
chemicals – the inflammatory agents.
These have vascular and neural effects.
The vascular effects are vasodilation
(causing calor and rubor) and increased
vascular permeability (causing tumor).
The neural effects involve either
activating or sensitizing nociceptors
(see below) and thus relate to pain
(dolor). These agents include potassium
ions, hydrogen ions, serotonin,
Dental Update – September 2001
O R A L
prostaglandins, neuropeptides,
adenosine, noradrenaline and various
cytokines.11 There is evidence that some
of these agents are present in inflamed
oral tissues, such as tooth extraction
sockets,12 TMJ13 and the periodontium.14
Activation of nociceptors
Nociceptors can be activated either
directly by the noxious stimulus itself or
indirectly by some of the chemicals in
the damaged tissue. In addition,
intradental nociceptors can be activated
indirectly by hydrodynamic
mechanisms.6 The chemicals that can
activate nociceptors are known as
algogenic (‘pain-producing’). Some
algogenic substances are released by
the injury while others are the result of
reactions triggered off in the damaged
tissue (Figure 1). Regardless of whether
a direct or indirect mechanism is
involved, one can assume that the
activation will involve an increase in the
membrane permeability of the nerve
ending, resulting in a depolarization,
which, if large enough, will generate
action potentials in the nerve fibres.
Sensitization of nociceptors
From personal experience we know that
damaged or inflamed tissues display
increased sensitivity, e.g. gentle
mechanical stimulation of inflamed skin
or a tooth with periapical inflammation
can cause severe pain. This
phenomenon, whereby pain is produced
by stimuli which would not normally do
so, is a type of hyperaesthesia called
allodynia. (Note: this condition used to
be known as primary hyperalgesia, but
the term hyperalgesia is now reserved
for conditions where increased
intensities of pain result from a stimulus
that would usually produce a lesser
level of pain.1) Allodynia is due largely
to sensitization of peripheral
nociceptors (cf. hyperalgesia, see
below) by inflammatory agents,
including the algogenic substances
when these are present in
concentrations that are too low to
produce a threshold depolarization
(Figure 1). However, sensitization does
B I O L O G Y
not happen equally in all nociceptors
(see above) and may apply only to some
of the types of stimuli that can excite a
particular nociceptor (e.g. mechanical,
heat).
Peripherally Acting Analgesics
The analgesic action of non-steroidal
anti-inflammatory drugs (NSAIDs) is
due to their ability to block synthesis of
the prostaglandins, which sensitize
nociceptors. They do this by inhibiting
the enzyme cyclo-oxygenase (COX).
There are two forms of this enzyme
(Figure 2):

COX-1 the constitutive (constantly
present) form, which is associated
with the physiological ‘protective’
role of prostaglandins;

COX-2 the inducible form, which is
associated mainly with inflammation
and pain.15
Selective COX-2 inhibitors are being
developed which ideally will have
analgesic and anti-inflammatory actions
without the undesirable side-effects that
are largely accountable to COX-1
inhibition (notably gastrointestinal and
haematological but also some renal and
respiratory).15
CNS PATHWAYS
The cell bodies of most orofacial
nociceptive neurons are in the trigeminal
ganglion and the central axons of all
three divisions project via the trigeminal
sensory root to synapse in trigeminal
nucleus caudalis (the hindmost part of
the so-called trigeminal spinal nucleus).
From here, second-order neurons project
to the thalamus from where third-order
neurons leave for the cortex (Figure 3).
Other cranial nerves, such as the
glossopharyngeal and some cervical
spinal nerves, can also contribute to
orofacial pain. There are at least two
types of second-order neurons in
nucleus caudalis that receive nociceptor
inputs:

nociceptive-specific cells receive
inputs only from nociceptors
361
 O R A L B I O L O G Y

A. Consciousness
Area X Area Y

Somatosensory
Cortex
Area X

Area Y

Thalamus

B. Consciousness
Area X Area Y

Noxious
Trigeminal Stimulus
Trigemino-thalamic Tract
nucleus
caudalis
CNS Area X

Area Y

Trigeminal PNS
Ganglion

C. Consciousness
Nociceptive
Area X Area Y
Nerves
Noxious
Stimulus

Area X
Nociceptors
Area Y
midline

Figure 3. Schematic representation of the pathway mediating signals
that result in pain from the orofacial region. Note that the second-
order neurons in the trigemino-thalamic tract cross the midline and
project to the contralateral thalamus; thus the sensation of pain is
generated on the opposite side of the brain to the injury that causes it.
Abbreviations: CNS, central nervous system; PNS, peripheral nervous
system.
Figure 4. (A) Divergence and convergence in nociceptive pathways.
Peripheral nociceptive nerves, before synapsing in the CNS, branch and
diverge to make contact with more than one second-order neuron. In this
way, information may ‘converge’ onto these second-order neurons. In this
theoretical model, the ‘straight-through’ pathways from the peripheral
nociceptors map on to corresponding areas within the ‘conscious’ parts of the
brain. (B) Radiating pain. If one of these nociceptive nerves is activated, it
may result in activation not only of its ‘own’ second-order neuron but also of
neighbouring ones (activated neurons shown in red). This can result in a
conscious perception that the pain is originating from a larger area (X+Y)
than it actually is (X). (C) Referred pain. Under certain circumstances, the
signal in the ‘straight-through’ pathway may not reach, or not be recognized
by, the conscious centres – the pain is then ascribed to the uninjured area (Y)
rather than the injured area (X). Again activated neurons are shown in red.

wide dynamic range (or
nociceptive-non-specific) cells
receive inputs from nociceptors,
mechanoreceptors and
thermoreceptors.
It seems that these neurons serve
different but complementary functions:
nociceptive-specific neurons may signal
the presence and location of a noxious
stimulus while the wide dynamic range
cells may grade its overall severity.16
Within nucleus caudalis the primary
afferent neuron terminals branch and
synapse with several second-order
neurons – the phenomenon of
divergence. Furthermore, each second-
order neuron receives inputs from many
primary afferents – the phenomenon of
convergence (Figure 4A). Convergence
and divergence of inputs may explain why
pains often ‘radiate’ and appear to arise
from a larger area than that which has
been injured or is diseased (Figure 4B). In
addition, neuronal convergence may
cause hyperalgesia (see above) in the
area surrounding an injury.
Neuronal convergence is also the
most likely explanation for referred pain,
whereby pain appears to come from a
structure other than the injured one
(Figure 4C). It is not clear why pains
should be misinterpreted in this way.
However, it seems possible that when
the consciousness receives signals
emanating from second-order neurons
that receive inputs from superficial and
deep structures, it interprets them as
originating from the more superficial
structure since such inputs normally
predominate.17 Thus, pain may be
referred from jaw muscles to the teeth or
from the teeth to the face18 but rarely if
ever in the opposite direction.
Second-order nociceptive cells in

362 Dental Update – September 2001

 O R A L B I O L O G Y

have roles in the emotional and motor

responses to pain.9 Some of these
A. projections are direct while others
involve an intermediate synapse in the
Primary Afferent 2nd Order Afferent reticular formation.
neurons neurons
Third-order neurons from the
"Gate"
ventrobasal thalamus project to the
primary somatosensory cortex. Other
nociceptive neurons project to other
B. Inhibitory
Interneurons
parts of the cerebral cortex, including
the secondary somatosensory cortex,
b
a the insula and anterior cingulate gyrus.
Recent studies using positron emission
+
tomography have shown that the
Primary Afferent 2nd Order Afferent anterior cingulate gyrus is the only
neurons neurons cortical area to be activated uniquely by
noxious thermal stimuli.19 Despite these
findings, the role of the cortex in pain is
poorly understood and complicated by
the facts that pain is still felt after
C. Aβ fibre ablation of large areas of cortex and that
mechanoreceptors it is difficult to produce pain by focal
+
+ electrical stimulation of cortical
structures.9
+
Aδ and C fibre
nociceptors DISCREPANCIES BETWEEN
INJURIES AND PAIN
Although pain often arises from obvious
causes (e.g. injury or disease), there may
Higher Centres be no clear relationship between the
D. degree of damage and the amount of
pain perceived:

Injuries causing severe tissue

damage do not always cause pain;
or the pain is not as intense as one
+ might expect. The classical examples
+ involve people wounded in battle or
injured on the sports field.
Aδ and C fibre
+
Pain sometimes occurs without any
nociceptors obvious tissue injury – e.g.
trigeminal neuralgia; thermal grill
Figure 5. The Gate Control Theory of Pain. (A) The concept. Signals carried by primary afferent illusions.19
nociceptive nerves must pass through a ‘gate’ before being passed on by second-order afferents in the
CNS. (B) The same scheme using the conventional shorthand for nerves. The primary afferent nerves Also, pain can be modified by many
excite (+) the second-order afferent neurons. The ‘gate’ is made up of small inhibitory interneurons (a,
factors in many circumstances. For
b), which can either reduce the amount of excitatory transmitter released by the primary afferents (a)
or directly inhibit the second-order neurons (b). The inhibitory interneurons themselves may be excited: example:
(C) by activity in adjacent large diameter mechanoreceptive nerves (‘segmental inhibition’), or (D) by
activity originating in higher centres in the CNS (‘descending inhibition’).
Procedures such as acupuncture20,
hypnosis21 and the placebo effect.22

Psychological considerations, such
nucleus caudalis project to the tract to synapse in the ventrobasal as individual and cultural factors, the
contralateral thalamus (Figure 3). Those nuclei. In addition, there are projections situation, its emotional impact, etc.23
concerned with the sensation of pain to the posterior and medial groups of
travel directly via the trigemino-thalamic thalamic nuclei, which are believed to It should also be borne in mind that

364 Dental Update – September 2001


surgical interruption of the presumed
nociceptive pathways does not always
permanently remove pain.24
These factors, amongst others, point
to the fact that pain is not the inevitable
consequence of action potentials
travelling to the central nervous system
along nociceptive nerves. However, it is
also clear that the discrepancies
between injury and pain do not result
simply from the conscious parts of the
brain ‘ignoring’ or ‘misinterpreting’ the
incoming signals. Rather it is because
nociceptive pathways are part of a
dynamic system in which neural activity
can be modified to suppress or enhance
the amount of pain that is experienced in
different circumstances. It is as if there
is some sort of ‘volume control’ in the
pathway linking the periphery with the
consciousness.
TRANSMISSION IN
NOCICEPTIVE PATHWAYS
Transmission at the first synapse in
nociceptive pathways is mediated by a
number of chemicals, including
glutamate, Substance P and calcitonin
gene-related peptide. These substances
are ‘excitatory’ in that they tend to
depolarize (and thus produce activity in)
the post-synaptic neurons. However,
these excitatory effects can be
decreased (‘inhibited’) by physiological
control mechanisms or enhanced
(‘facilitated’) under certain – often
pathological – circumstances.
Inhibitory Controls
The inhibitory controls that modulate
activity in nociceptive pathways (Figure
5) are often referred to as gate controls.
The Gate Control Theory of Pain was
first proposed in 1965 by Melzack and
Wall.25 Although many of the details of
the original model have been modified
as knowledge has increased, the
concept has endured because it is
consistent with both clinical
observations of pain and laboratory
findings regarding nociceptive
mechanisms. The principle (Figure 5A)
is that the signals passing from primary
afferent nociceptive nerves to second-
Dental Update – September 2001
O R A L
order cells (in the spinal cord or the
trigeminal system) have to pass through
a ‘gate’, which may be wide open (in
which case the resulting pain may be
severe), closed (in which case no pain
will be felt) or, most commonly, partly
open. In practice it seems that the ‘gate’
consists of interneurons which can
inhibit activity beyond the first synapse,
either by decreasing the release of the
excitatory transmitters (presynaptic
inhibition) or by inhibiting the second-
order cells (postsynaptic inhibition)
(Figure 5B). These inhibitory effects are
mediated by a variety of agents,
including γ-amino butyric acid (GABA),
glycine and endogenous opioid
peptides such as enkephalins and
dynorphins. The interneurons
themselves may be activated either by
signals in other afferent nerves or by
signals descending from the brain.
These mechanisms are outlined below
but readers may wish to refer to more
detailed reviews.8
Activation of Gate Control Interneurons by
Other Primary Afferent Neurons
There is ample evidence that activity in
large diameter (Aβ) afferent nerves from
the same neural segment of the body
can inhibit activity in second-order
nociceptive neurons (Figure 5C). Since
the vast majority of Aβ nerves are
mechanosensitive, these segmental
inhibitory controls can be activated
naturally by rubbing close to an injury
(or a diseased tooth). From a clinical
standpoint it is worth considering that,
under normal circumstances, these
controls will almost always be active to a
limited extent (given that mechano-
receptors are constantly being excited by
our movements). Thus anything that
reduces mechanoreceptive activity from
part of the body is likely to increase the
sensitivity of that area for pain by
‘opening the gate’. For example, this
might occur after pressure damage to a
nerve (Aβ fibres are amongst the most
easily damaged by physical insult) or
when a patient reduces movement of a
chronically painful region. This may
explain why re-establishing normal
mobility can contribute to the successful
treatment of some chronic pains.
B I O L O G Y
A
Increased transmitter release from
pre-synaptic neuron*
Increased expression of receptors on
post-synaptic neuron
Enhanced post-synaptic depolarization*
Metabolic changes in post-
synaptic neuron
B
Figure 6. Central sensitization. The effects of
afferent nerve input (A) on a post-synaptic
neuron (B) can be enhanced in several ways.
These mechanisms may be triggered by
persistent nociceptive inputs or by damage to
peripheral nerves. The facilitatory mechanisms
marked * may also be produced by the removal
of inhibitory influences.34
Knowledge of these segmental
controls gave rise to the principle of
transcutaneous electrical nerve
stimulation – TENS26 – whereby
selective activation of Aβ nerves with
electrical stimuli has been used to
relieve pain. This concept has also been
exploited in various forms of so-called
electronic dental analgesia, although
these are not always successful.27
It should be noted that not all forms
of TENS work via Aβ fibres acting
segmentally. In particular, when TENS is
used at relatively high intensities it may
exert its effects via descending
pathways (see below).
Activation of Gate Control Interneurons by
Pathways Descending from Areas in the
Brain
Electrical stimulation of sites in the
brain (Figure 5D), and particularly the
brainstem, (e.g. the periaqueductal or
periventricular grey matter, the raphe
nuclei) can produce analgesia, and
inhibit the responses of second-order
nociceptive neurons. It is generally
assumed that the underlying
mechanisms again involve activation of
interneurons mediating the gate
controls – on this occasion by nerve
fibres descending from the brain
(Figure 5D). In addition, some of the
descending pathways may directly
inhibit the nociceptive pathways (i.e.
without the intermediary interneurons).
365
 O R A L B I O L O G Y

Facilitation
In contrast to the inhibitory controls
described in the previous section, the
Somatosensory transmission of signals at the first
Cortex synapse in nociceptive pathways may
also be increased (‘facilitated’). When
general anaesthetics, such a ‘gain’ occurs in the nociceptive
hypnotic analgesia system, the effect is to increase the
strength and/or duration of the resulting
Thalamus pain. The most studied example of this is
the phenomenon of wind-up, whereby
narcotic analgesics, repetitive activation of nociceptive C-
electrical stimulation systems fibres brings about an enhanced
(TENS, EDA), response to subsequent activity in
counterirritation
these fibres.29 Wind-up may be brought
about by a number of factors, including
Trigeminal Trigemino-thalamic Tract
increased release by presynaptic
nucleus neurons of transmitters such as
caudalis
CNS Substance P, and increased
responsiveness of post-synaptic
receptors for Substance P (NK1
Surgical
receptors) and glutamate (NMDA
Trigeminal interruption PNS
Ganglion
receptors).30 The mechanisms of wind-
up may be similar but not identical31 to
those responsible for ‘long-term
potentiation’ that is believed to underlie
Nociceptive
some forms of learning and which also
Nerves results from repeated activation of
local anaesthetics NMDA receptors, notably in the
hippocampus.32 Indeed, it has been
suggested that wind-up may contribute
to the development of a ‘pain memory’
Nociceptors
at lower centres of the nervous
midline system.30
e.g. simple analgesics Perhaps more immediately relevant
(e.g. NSAIDs), than wind-up from a clinical perspective,
topical anaesthetics are the central sensitization
phenomena33,34 that occur in response to
Figure 7. Sites of action of pain control procedures. The most common means of controlling pain (blue
arrows) act primarily (but not exclusively) at the indicated points in the nociceptive pathways. Other persistent nociceptive inputs and to
classes of drug used in the control of orofacial pain – including antidepressants and membrane- peripheral nerve injuries. These can
stabilizing drugs (e.g. carbamazepine) – may have several sites of action, and for clarity of involve one or all of the processes
presentation these are not shown here. In addition, some forms of intractable pain are sometimes shown in Figure 6. Central sensitization
treated by surgically interrupting these pathways – most often at the points indicated by the green may contribute to hyperalgesia and
arrows.
some forms of allodynia (see above).
There is one other – recently
The descending fibres involved usually stimulus in another part of the body. discovered – mechanism that may
release the monoamine transmitters, enhance activity in central nociceptive
serotonin (5-HT) and noradrenaline. The first of these may explain the pathways with potentially enormous
It is not entirely clear how these reduced levels of pain felt in battle or on consequences for our understanding of
pathways are activated naturally but the sports field (see above) while the pain. Studies in vitro have shown that
there is evidence that this may occur latter is almost certainly the basis for some mammalian neurons, which may be
under at least two different counter-irritation phenomena28 whereby second-order nociceptive cells, have
circumstances: ‘one pain masks another’. It is possible intrinsic properties that allow them to
that some traditional methods for pain behave in a fashion which electrical

conditions of stress or anxiety; control, such as acupuncture, may be engineers would describe as bistable,

when there is a noxious/painful forms of counter-irritation. i.e. once these cells are depolarized by a

366 Dental Update – September 2001


transient excitatory influence they
remain partially depolarized until
subjected to a transient inhibitory
influence.35 This mirrors previously
reported patterns of activity in such
neurons in vivo36 and may be
fundamental to our understanding of
how many clinical pains outlast the
injuries that initially produce them.
CONTROL OF PAIN
It is important to understand that the
various means by which we control pain
act at different parts of the nociceptive
pathways that we have discussed in this
paper (Figure 7). In this regard, it may be
noted that the neurochemistry of the
inhibitory controls and facilitatory
phenomena is only gradually being
unravelled. It offers exciting possibilities
for the development of new, centrally
acting analgesic drugs, to augment
those currently available.
R EFERENCES
1. Merskey H, Bogduk N, eds. Classification of
Chronic Pain, 2nd edn. IASP Task Force on
Taxonomy. Seattle: IASP Press, 1994; pp.209–
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