01 - Chapter - Sympathetic Nervous System and Pain
01 - Chapter - Sympathetic Nervous System and Pain
01 - Chapter - Sympathetic Nervous System and Pain
1
Sympathetic
nervous system
and pain
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A CLINICAL OVERVIEW
1
A clinical overview of the
autonomic nervous system,
the supply to the gut and
mind–body pathways
Introduction
The autonomic nervous system (ANS) is an ‘output’, ‘effector’ or ‘motor’
system (see Gifford 1998b)—i.e. it responds to the demands of the sensory
systems and the central nervous system (CNS) by producing an effect on the
tissues it supplies. There are no sympathetic or parasympathetic sensory
(afferent) fibres as such, although a great many visceral sensory fibres do
travel in nerves like the vagus and splanchnic, which are commonly described
in parasympathetic and sympathetic sections of anatomy texts and often
referred to as ‘sympathetic afferents’ (see discussion of visceral afferents
below).
Since the ANS is an output system, its role in pain states has to be
secondary to its effects on sensory systems (see following chapters).
ANS fibres create their ‘effects’ via electrochemical stimulation of smooth
muscles or glands. Their secretions also produce direct chemical effects on
the tissues they innervate and thus change their chemical characteristics.
Any chemical or physiological tissue changes may in turn be fed back to the
CNS via stimulation of sensory afferent pathways. This is important because
ANS activity has been implicated not only in producing and modulating
nociception and pain, but also as playing a role in the expression and
conscious awareness of emotions (see Meyers 1986). Recent studies show,
for example, that different emotions (anger, fear, disgust, sadness, happiness,
surprise) can be distinguished to some extent on the basis of different
autonomic nervous system responses (like skin temperature and heart rate)
(LeDoux 1998, p 292). We all know that strong emotions are expressed as
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bodily sensations and that ‘gut feelings’ play crucial roles in our emotional
experiences and can have a strong impact on our decision making processes
(Damasio 1995, LeDoux 1998, Damasio 2000).
In their detailed overview of the ANS, Janig and Habler (1999) go out of
their way to debunk the traditional descriptions of the ANS and the view
that it is ‘all or nothing’ and general in its mode of action. In parallel with the
neuroendocrine system, the ANS regulates target organs in order to maintain
the homeostasis of the body. Simply, it adapts, adjusts and co-ordinates
appropriate systems so as to produce the required physiological conditions
for life, which includes, any required physical activity. In this way it is
involved in producing and co-ordinating the necessary physiological
responses for activities like moving, resting, sleeping, feeding and digestion,
sex, pregnancy and nurturing, growth and repair and all extreme responses
relating to threatening and stressful situations. This includes responding to
tissue injury and to pain.
Neocortex
Limbic
system
Hypothalamus
Neuro Autonomic
Skeleto-
endocrine nervous
motor
system system
system
Body
organs External
world
Fig. 1.1 A modified version of Janig and Habler’s model of the integration and
relationships of the brain and body. What it so nicely illustrates are the forward and
back communication links between all levels of the nervous system, the body, and the
environment. Communication is via neuronal, hormonal and humoral pathways.
Adapted from: Janig W, Habler HJ 1999 Organization of the autonomic nervous system: structure
and function. In: Appenzeller O (ed) Handbook of Clinical Neurology Vol 74 (30): The Autonomic
Nervous System Part 1: Normal Functions. Elsevier, Amsterdam
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It is often said that the sympathetic system ‘kicks into action during
emergencies’. Robert Salposky (1994) adds the (clinically) important caveat
‘or what you think are emergencies’—that underlines the importance of
personal assessment of the situation we find ourselves in. Thus, how the
sympathetic system responds is very much influenced by the emotional,
cognitive and conscious brain—‘our’ interpretation of the situation we are in
is hugely responsible for its activities. If you believe the pain you have signifies
a serious illness or condition you will have a far different ‘sympathetic’ reaction
than if you dismiss the pain and pass it off as trivial. If as a patient you think
that what the therapist is doing to you makes sense and feels right you will
have quite a different response from someone who might be feeling unsure or
even slightly anxious about what is being done to them (see also Chapter 4). It
is probable that a clinician’s most powerful effect on a patient’s sympathetic
system activity is produced via the atmosphere of the therapeutic interaction.
Importantly, this relates more to what the patient actually feels and interprets,
than to what the clinician thinks they should feel or should have interpreted.
The effect of a productive ‘therapeutic alliance’ on the activities of systems
like the ANS should never be underestimated (see the Placebo section in Topical
Issues in Pain 4.)
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A CLINICAL OVERVIEW
Fig. 1.2 The thoracic paravertebral sympathetic chain and its relationships
Adapted from: Harati Y, Machkhas H 1997 Spinal cord and peripheral nervous system. In: Low PA
(ed) Clinical Autonomic Disorders 2nd edn. Lippincott-Raven, Philadelphia
The best known parts of the sympathetic system are the two sympathetic
chains or trunks that extend from the base of the skull to the coccyx. These
two ‘paravertebral’ sympathetic chains lie on either side of the vertebral
column (Figs 1.2, 1.3, 1.4 & 1.5) but may come together and fuse in the sacral
region to form the ganglion ‘impar’. Each chain has about 22 or 23
paravertebral ganglia which contain nerve axons and the cell bodies of
postganglionic neurones. A ganglion is a swelling of a nerve due to the large
numbers of cell bodies it contains. Sympathetic ganglia can be thought of as
communication boxes or relay stations where information in the form of
impulses may be modulated and passed on, even prevented from passing
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Fig. 1.3 The organisation, layout, relations and basic supply of the peripheral
sympathetic system. Dashed lines represent preganglionic fibres, continuous lines
represent postganglionic fibres.
Adapted from: Harati Y, Machkhas H 1997 Spinal cord and peripheral nervous system. In: Low PA
(ed) Clinical Autonomic Disorders 2nd edn. Lippincott-Raven, Philadelphia
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A CLINICAL OVERVIEW
Fig. 1.4 The origin and course of the sympathetic fibres to the arm. The diagram also
shows the cervical sympathetic chain, roots and brachial plexus relationships. The
preganglionic fibres from T2 and T7 are dotted because their supply to the upper limb
is uncertain. The preganglionic fibres from T1 and T8 are dashed to show they are
present but not involved in the upper limb sympathetic supply. The cervical roots have
no preganglionic fibres and the spinal nerves of the plexus that derive from these roots
only have grey rami communicantes. SCG: superior cervical ganglion; MG middle cervical
ganglion; SG stellate ganglion.
Adapted from Grieve GP 1994 The autonomic nervous system in vertebral pain syndromes, Fig.
20.4. In: Boyling JD, Palastanga N (eds) Grieve’s Modern Manual Therapy 2nd edn. Churchill
Livingstone, Edinburgh
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Fig. 1.5 The sympathetic supply to the lower limbs following the principle of Fig. 1.4.
The parasympathetic supply is also illustrated.
Adapted from Grieve GP 1994 The autonomic nervous system in vertebral pain syndromes, Fig.
20.5. In: Boyling JD, Palastanga N (eds) Grieve’s Modern Manual Therapy 2nd edn. Churchill
Livingstone, Edinburgh
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with the first thoracic ganglion. There are usually four ganglia in the lumbar
part of the chain and four or five in the sacral region.
The spinal cord only connects to the sympathetic chain via the 14 spinal
nerves that exit from the intervertebral foramen between T1 and L3 (i.e. via
roots T1–L2) (Figs 1.3, 1.4, 1.5). Hence its ‘outflow’ is said to be ‘thoraco-
lumbar’. This means that all the peripheral sympathetic nerve pathways to
the target tissues and organs of the body have their origins in the spinal cord
segments of T1 to L3 (but see Grieve 1994, p 297).
Although it has segmental origins, the SNS, to quite a marked extent,
actually defies the traditional description of a segmental system (see below).
Thus, sympathetic supply to the head and neck has its origins from the nerve
roots of T1–T5 (mostly upper 2 or 3); the upper limb from roots T2–T6 (but
possibly as far as T7 or T8) (Fig. 1.4); the thorax from roots T3–T6; the abdomen
from roots T7–T11 and the lower limbs from roots T10–L2 or L3 (Fig. 1.5).
This supply may be an important consideration when investigating the
consequences of thoracic and high lumbar nerve trunk and nerve root injuries
or irritations. What can be applauded is the neat fact that these vital control
supply lines exit and have their origins from parts of the spinal column that
are relatively rarely injured and well protected.
The sympathetic supply involves a two neurone pathway from the spinal
cord to the target tissues of the periphery (Fig. 1.6). These neurones are termed
preganglionic and postganglionic respectively.
There is some evidence that the sympathetic ganglia contain inter-
neurones, termed ‘SIF’ (small intensely fluorescent) cells that may serve
modulatory functions, i.e. they aid in the integration or processing of
incoming and outgoing information (see Grieve 1994, p 299).
The preganglionic neurones of the sympathetic system have their cell
bodies in the lateral grey horn (Fig. 1.7), (also known as the intermediate
zone, or interomediolateral cell column) of the spinal cord. As already noted,
the cell bodies of these neurones are only found in segments T1 to L3
(Westmoreland et al 1994) of the spinal cord. Its segmental origins are worth
noting since the sympathetic system innervates just about every tissue of
the body via these spinal segments.
Myelinated preganglionic fibres pass away from the spinal cord via the
ventral root and into the spinal nerve for a short distance, then via the white
rami communicantes they join the sympathetic trunk.
Having reached the sympathetic trunk, the preganglionic sympathetic
fibres may do several things (see Fig. 1.7). Some synapse with postganglionic
cells in the paravertebral ganglion that lies at the same level from which they
exit the vertebral column (nos 1, 3 & 4 in Fig. 1.7). Others pass through their
segmental ganglion and run up or down to more distant paravertebral ganglia
where they terminate and synapse with postganglionic fibres (no. 5 in Fig.
1.7). Note how this defies the idea of ‘segmentalism’. It is commonly stated
that there is a pre to postganglionic neurone divergence ratio of anything
from 1:1 to 1:196 (see Grieve 1994, Williams et al 1995). In other words one
preganglionic fibre may terminate with only one postganglionic fibre, or
may have a massive terminal aborisation connecting to a great many. The
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Fig. 1.6 The basic arrangement of the peripheral components of the sympathetic
and parasympathetic systems. Note the long to short relationship of the pre to post
ganglionic sympathetic fibres and the opposite for the parasympathetic fibres. Cranial
outflow of the parasympathetic system not illustrated here. Classic neurotransmitters
and receptor types for each system are illustrated: A-r adrenoreceptor; mr muscarinic
receptor; n nicotinic receptor; N-a noradrenaline/norepinephrine; Ach acetylcholine.
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Adapted from: Harati Y, Machkhas H 1997 Spinal cord and peripheral nervous system. In: Low PA
(ed) Clinical Autonomic Disorders 2nd edn. Lippincott-Raven, Philadelphia
tissues. The fact that there may be provision for control of this divergence
helps explain a degree of specificity, too.
In a similar way to that described in the CNS, the potential for excessive
reactivity and spread of effect due to maladaptively altered modulatory
controls, or even loss of control, having far reaching effects on sympathetic
activity seems a reasonable possibility. Clinically this may provide a possible
explanation for reports of localised patches of skin colour change, or localised
sweating or swelling disturbances that spread to larger areas over time.
Many preganglionic fibres pass right through the sympathetic chain and
paravertebral ganglia without synapsing on postganglionic fibre cells at all
(no. 2 in Fig. 1.7). These continue out of the sympathetic chains in the
splanchnic nerves to reach remote ganglia situated nearer their target organs.
These more distant ganglia are often called ‘prevertebral’ ganglia (Figs 1.3,
1.7). Well known prevertebral ganglia supplied via the thoracic splanchnic
nerves are the celiac, superior and inferior mesenteric ganglia. These ganglia
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are situated in the abdomen anterior to the abdominal aorta close to the origin
of the celiac and mesenteric arteries. Via postganglionic fibres they form the
celiac plexus that innervates abdominal, pelvic and perineal organs. While
the thoracic splanchnic nerves derive from branches arising from the lower
eight thoracic paravertebral ganglia, the lumbar splanchnic nerves derive from
branches arising from the upper three lumbar paravertebral ganglia.
One special group of preganglionic neurones pass directly to their target
tissue (see Fig. 1.3). These innervate the adrenal medulla, seemingly omitting
the ‘postganglionic’ component of the pathway. In fact, the adrenal medulla
resembles nervous tissue more than it does a typical endocrine gland. Its cells
behave like neurones and derive embryologically from postganglionic
sympathetic cells. These adrenal medulla cells secrete adrenaline (epinephrine)
and noradrenaline (norepinephrine) into the circulation in response to SNS
activity that derives from situations that are exciting or stressful, or that are
anticipated to be exciting or stressful. This is an excellent example of how
mind influences body and can easily be translated to the clinical encounter!
Postganglionic fibres have their cell bodies in the autonomic ganglia
described above. Their unmyelinated axons radiate to the target tissues. Those
postganglionic fibres that have their origins in the ganglia of the paravertebral
sympathetic chain follow three main courses:
1. Pass back into the spinal somatic nerve trunk via grey rami
communicantes (no. 4 in Fig. 1.7). Some apparently may pass back in via
the white rami communicantes, too (Janig & Habler 1999). From there,
the fibres travel in the peripheral nerves to supply the target tissues, for
example, the blood vessels (vasomotor), and sweat glands (sudomotor)
in the territories of the nerves they accompany. Thus, postganglionic axons
from the cervical ganglia innervate upper extremity tissues by entering
the cervical spinal nerves of the brachial plexus deriving from C4–C8,
and following the peripheral nerve trunks (see Fig. 1.4). Grey rami
communicantes in the neck may pierce and travel through the longus
capitis or the scalenus anterior muscles—a fact that may be an important
consideration in whiplash injury (see Thacker 1998). Clearly, if these grey
rami are injured it may mean the loss of sympathetic supply and control
to blood vessels and tissues of the arm.
2. Pass to blood vessels in the neighbourhood of the sympathetic trunk (no.
3 in Figs 1.7 and 1.2, 1.4, & 1.5) and supply these or travel along with
them to reach more distal targets. For example, axons from the superior
cervical ganglion innervate the pupil of the eye and provide sweat gland
innervation of the face by following the course of branches of the internal
and external carotid arteries to get there.
3. Pass to visceral organs. For example, postganglionic fibres whose origins
are in the lower cervical and upper thoracic ganglia innervate the heart
via the cardiac plexus to produce cardiac stimulation, or reach the
tracheobrachial tree via the pulmonary plexus to control bronchodilation
(we need more efficient lungs when we are about to perform physically,
e.g. as in competition or combat).
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Clinical implications
Some clinically related points:
1. It is important to emphasise that all peripheral nerves contain sympathetic
post ganglionic fibres and that they enter the nerves via grey rami
communicantes.
This means that those somatic nerves that derive from nerve roots above
T1 (including many cranial nerves) and from roots of L3 and below, still
receive their supply via grey rami communicantes but will have no white
rami communicantes (Figs 1.4 & 1.5). Think about it and you realise that all
the cervical nerve roots and those roots below L3 will have no sympathetic
neurones. The sympathetic nerve fibres join the spinal nerves outside the
intervertebral foramen. This may well be an important clinical/diagnostic
consideration. For example, it may explain the common clinical finding that
classic acute and sub-acute nerve root disorders in these regions show no
signs of classic ‘sympathetic abnormality’ when compared to patients with
symptoms attributable to nerve injury beyond the root level, or from levels
where roots contain sympathetic fibres. It has been suggested that the
tortuous routes taken by sympathetic fibres may in itself present a greater
potential for trauma and irritation (Pick 1970).
2. As stated earlier, the cervical ganglia contain preganglionic fibres that
may have their origins from nerve roots as low as T8.
This means that injuries or irritations of nerve roots in the upper and
middle thoracic regions can have effects in the arms and head as well as in
the viscera and somatic tissues more locally. Clinical investigations of upper
extremity oedema, skin health, changes in circulation, changes in temperature
or sweating must consider possible root origins in the thoracic spine.
3. The major sympathetic vasoconstrictor supply to the upper limb arteries
derives from roots T2 and T3.
The vasoconstrictor supply reaches the upper limb arteries via branches
from the brachial plexus. This beautifully illustrates the complex anatomical
routing of the sympathetic supply—from spinal cord, to ventral root of T2
and T3, into the ventral ramus, out via the white rami communicantes into
the sympathetic chain—then synapsing with postganglionic fibres that course
into the brachial plexus via grey rami communicantes before continuing on
in the peripheral nerves to their vascular destinations. Changes in skin
temperature and circulatory perfusion of the arm associated with
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Fig. 1.8 The organisation, layout, relations and basic supply of the peripheral
parasympathetic system. Dashed lines represent preganglionic fibres, continuous lines
represent postganglionic fibres.
Adapted from: Harati Y, Machkhas H 1997 Spinal cord and peripheral nervous system. In: Low PA
(ed) Clinical Autonomic Disorders 2nd edn. Lippincott-Raven, Philadelphia
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also, that chemical agents that activate the receptors are called ‘agonists’
and that ‘antagonists’ block the receptors and hence prevent their activity.
Phentolamine, discussed in Chapter 4, is an example of an adrenoreceptor
antagonist commonly used in the diagnosis and management of
sympathetically maintained pain.
Readers interested in a more detailed account of the neurochemical
organisation of the autonomic nervous system are advised to consult Milner
et al (1999).
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Habler 1995). Clearly, the viscera has a relatively poor sensory supply
when compared to the skin, where the supply is vast, or the deep somatic
domain, where it is more modest than the skin, but still significant
compared to the gut. As discussed below visceral primary afferents may
send collateral branches to sympathetic postganglionic efferents in the
prevertebral ganglia.
2. Visceral afferents that travel to the CNS via cranial nerves and terminate
in appropriate brain nuclei. For example, central endings of afferents
travelling in the vagus nerve mainly terminate in the nucleus of the solitary
tract (NST) that lies in the brain stem. Ritter et al (1992) state that 80–85%
of nerve fibres in the vagus nerve are afferent fibres.
Just like somatic sensory fibres, there are several functional subtypes of
spinal and cranial visceral afferents. These are discussed in relation to
visceral pain in the section following.
3. ‘Enteric’ visceral afferents (Fig. 1.9). These afferents lie in the walls of the
gut and communicate with enteric interneurones and motor neurones as
well as sending branches to prevertebral ganglia where they synapse with
postganglionic fibres of the autonomic system.
Visceral primary afferents continually sample the state of affairs in their
target organs. Hence information about such things as the contents of the
gut, bladder, colon, and the chemistry of the blood may be relayed centrally
for processing and the generation of appropriate responses. Higher centres
and ‘consciousness’ may become involved; we well know that situations in
the viscera often promote physical action, such as when our bladder or bowel
is full, when we are dehydrated, when we are hungry or satiated, and when
sexually aroused. However, for many of the mundane operations that go on
in the gut there is little need for conscious or subconscious analysis. Much
activity and control goes on far nearer the tissues themselves.
Several ‘levels’ of integrative control have been identified:
1. At the lowest integrative control level sits the enteric nervous system of
the gut. Here, the neural organisation illustrates its isolated ‘sample —
scrutinise — response’ capabilities and hence, its special autonomy.
2. A second integrative level consists of a local control loop involving
postganglionic autonomic fibres. Here, collateral branches of centrally
projecting primary afferents as well as projections from visceral afferents
of the enteric system (Fig. 1.9) synapse with postganglionic sympathetic
fibres in the prevertebral ganglia. Hence, the formation of an ‘extraspinal’
reflex feedback loop. Regulation at this level is said to be via ‘extracentral
reflexes’ since they can operate without involving the CNS, though they
may well be influenced by modulating central inputs. These reflexes are
thought to be important in control and regulation of gut motility
(enhancement of peristalsis, storage function), regulation of fluid
(excretion), as well as in protection. ‘Protection’ or protective reflexes that
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Fig. 1.9 The enteric nervous system and the afferent and efferent pathways between
the gut and the spinal cord. Note how the postganglionic fibre activity can be modulated
by visceral afferents going to the spinal cord as well as by gut visceral afferents that
send branches to the postganglionic cell body.
Adapted from: Janig J, Habler, HJ 1995 Visceral-autonomic integration. In: Gebhart GF (ed) Visceral
Pain. Progress in Pain Research and Management Vol. 5. IASP Press, Seattle
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Fig. 1.10 Shaded areas show zones of pain referral felt when organs indicated are
diseased/inflamed.
Adapted from: Westmorland et al 1994 Medical Neurosciences 3rd edn. Little Brown, Boston
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Some points
Stressful situations activate the SAM axis resulting in the fight or flight
response and associated feelings of anger and anxiety.
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cancer and heart disease. On a positive note is the evidence that some coping
strategies can minimise the detrimental effects of stressful life events; that
positive emotional states can enhance immunity (for all references see
Watkins 1997), and that some people’s poor coping strategies can be shifted
into more helpful and health promoting ones.
Clinicians are urged to consider the potentially massive positive psycho-
physiological impacts that can be achieved as a result of treatment encounters,
and that the ANS is regarded as a major efferent pathway linking mind and
body.
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