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240 Kwok Fu Jacobus NG
system injury or damage and poor response to
conventional analgesics such as non-steroidal anti-
inflammatory agents (NSAIDs) and opioids.
On examination, there may be signs of motor,
sensory or autonomic nervous system dysfunction
in the area of pain or in adjacent sites. Some of
these are rather characteristic, such as autonomic
dysfunction resulting in abnormal vasomotor and
sudomotor activities in patients with complex
regional pain syndromes (see below). e signs of
allodynia, anaesthesia dolorosa and hyperpathia are
all characteristic of neuropathic pain.
Some of the symptoms and signs reveal clues to
the pathophysiological mechanism underlying the
patient’s pain. For example, a more constant type
of pain usually suggests the presence of significant
central sensitisation. Paroxysmal spontaneous
pain of brief duration can be explained by ectopic
impulse generation, whereas paroxysmal evoked
pain such as allodynia may be related to cross
excitation or nociceptor sensitisation.
e mainstay of treatment in neuropathic
pain is systemic analgesics. Nerve blocks and
neurodestructive procedures are only useful in
conditions caused by an anatomically distinct
lesion, such as trigeminal neuralgia [79].
Neuroaugmentation may be useful in some
conditions [81], particularly when the pain has an
ischaemic element [78]. When systemic analgesics
are used, it is generally believed neuropathic
pain conditions are not opioid responsive. e
classical drugs used in treatment of neuropathic
pain include tricyclic antidepressants such as
amitriptyline, classical anticonvulsants such as
carbamazepine [75] and systemic lignocaine [49].
Newer agents that have shown promise include the
anticonvulsant gabapentin, which has been found
useful in diabetic neuropathy [3] and postherpetic
neuralgia [67]. N-methyl-D-aspartate antagonists
represent the latest development in the treatment
of neuropathic pain, but their efficacy needs to be
further evaluated.
Although traditionally opioids have been considered
ineffective, most recent studies have found them
useful in treating neuropathic pain [19, 70, 88].
Tramadol, an opioid with low abuse potential and
some monoaminergic activity, may be particularly
useful in this aspect [75].
More details of individual drugs and
neuroaugmentation can be found in Chapter 10
and Chapter 8 respectively.
Classication of neuropathic
pain syndromes
ere are many pain syndromes which are
neuropathic in nature. ere are also numerous
classification methods. e IASP classification
combines classification by involvement
(generalised versus localised), by anatomical site
(head and neck, upper limb, lower limb, etc.),
by pathological process if known (infective,
inflammatory, trauma, vascular, etc.) and finally
by the initial insult if there is no longer an active
pathological process accompanying the pain
Table 15.02 Common neuropathic pain syndromes
Generalised syndromes
• Peripheral neuropathy — diabetic, AIDS,
neurofibromatosis, etc.
• Stump pain
• Phantom pain*
• Complex regional pain syndrome, Type I (CRPS
I)*
• Complex regional pain syndrome, Type II
(CRPS II)*
• Central pain*
Localised syndromes
Head and neck
• Trigeminal neuralgia
• Trigeminal postherpetic neuralgia
• Glossopharyngeal neuralgia
• SUNCT syndrome (Shortlasting, Unilateral,
Neuralgiform Pain with Conjunctival Injection
and Tearing)
Limbs
• Brachial plexus avulsion
• Post-irradiation pain of brachial plexus
• Carpal tunnel syndrome
• Spinal and radicular pain
• Fracture-related radicular pain
• Infection-related radicular pain
• Tumour-related radicular pain
• Arthritis-related radicular pain
Chest and abdomen
• Postherpetic neuralgia*
• Segmental or intercostal neuralgia
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Neuropathic Pain 241
other than the pain pathophysiology itself (e.g.
phantom pain and central pain). is is the
most widely accepted classification but is also
extremely complicated. Table 15.02 lists the
more commonly encountered clinical syndromes
within their IASP classes. e reader should refer
to the original IASP document (Classification
of Chronic Pain, 2nd Edition, 1994) [52] for a
more complete list.
e syndromes more commonly encountered in a
pain clinic are listed with asterisks and discussed in
detail following table 15.02.
Important Syndromes
Postherpetic neuralgia
ere is no universally accepted definition of how
long pain needs to persist after an attack of acute
zoster before a patient can be labelled as having
postherpetic neuralgia (PHN). A useful working
definition is the persistence of pain beyond the
crusting of the lesions and lasting more than 2 months
from the onset of the lesions [90]. Conformity in
definition is important for the critical appraisal of
the numerous clinical trials and anecdotal reports
in the literature concerning treatment of PHN. e
lack of conformity in definition may account for a
considerable proportion of the conflicting results
seen in these reports.
e incidence of PHN is two to four cases per 1,000
population per year. Overall, about 10% of all
patients who develop acute zoster infection progress
to PHN. e incidence rises sharply with age, and
patients over 70 years of age are approximately 10
times more likely to develop PHN compared with
those aged below 20 years. e condition is slightly
more common in males. Immunocompromised
patients (e.g. with AIDS or cancer) are also more
likely to develop PHN. e usual duration of PHN
is months to years. Postherpetic neuralgia gradually
improves in most patients, and spontaneous
subsidence is not uncommon.
Clinically, the pain is usually severe, constantly
present with exacerbations. Postherpetic neuralgia
is characteristically exacerbated by mechanical
contact. In 50% of patients, the thoracic dermatomes
are affected. e trigeminal distribution (especially
V1) is next, followed by cervical and lumbar
dermatomes. Diagnosis is usually straightforward.
It is important to note that a high proportion of
patients with PHN are depressed, and suicide has
been reported occasionally.
e most striking pathology in PHN is the loss of
large fibres in affected sensory nerves. In addition,
chronic inflammatory changes are also seen in the
dorsal root ganglion and demyelination is seen in
the root entry zone. ese changes presumably
reduce the peripheral inhibitory mechanisms and
are responsible for some of the pain experienced in
PHN. is also explains why elderly patients, who
generally have smaller numbers of large fibres, are
more vulnerable to the development of PHN.
In young patients, oral tricyclic antidepressants such
as amitriptyline should be the first-line treatment.
Both gabapentin [66, 67] and pregabalin [22, 26,
71] have been found to show promising results in
PHN. In elderly patients, it is prudent to consider
the many side effects of tricyclic antidepressant
treatment, such as the anticholinergic effects,
orthostatic hypotension and sedation. Generally,
topical treatment is recommended as the first-line
treatment in the elderly.
Many topical preparations have been proven
effective in PHN. Capsaicin 0.075–0.1% applied
topically three to four times daily is highly
effective in some patients [7]. Other patients find
the initial burning with capsaicin intolerable and
cannot endure this treatment [89]. Topical local
anaesthetics are readily available and useful in
some patients (EMLA® cream, a eutectic emulsified
mixture of 2.5% lignocaine and 2.5% prilocaine;
or Lidoderm®, a 5% lignocaine gel). ey may be
applied as a thin layer three to four times a day, or
as a thick application under an occlusive dressing
[68, 69]. e method of application depends on
the area involved and patient’s preference. Topical
NSAIDs such as 3% benzydamine cream five to
six times a day, or crushed acetylsalicylic acid 750–
1500 mg mixed with diethyl ether or chloroform
applied topically three times a day [18] have
also showed some promise. Systemic side effects
of NSAIDs should be minimal unless the area
involved is extensive.
Other drugs which have been reported to be
helpful in PHN include anticonvulsants such as
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242 Kwok Fu Jacobus NG
carbamazepine, alpha-2 agonists such as clonidine
[50] and local anaesthetic-type drugs such as
mexiletine. ese drugs taken orally should be used
in conjunction with topical treatment. As indicated,
it is better to start with topical applications in
elderly patients and with oral preparations in
younger patients.
For more resistant cases, the next line of treatment
to consider is epidural steroid injection [24],
together with local anaesthetics. Acupuncture
and transcutaneous electrical nerve stimulation
(TENS) can also be tried as they involve minimal
risk to the patient. Neurolysis of the nerves
affected, using chemicals such as phenol or
alcohol, or by radiofrequency or cryotherapy, is
only rarely effective. Spinal cord stimulation and
surgical procedures, such as dorsal root entry zone
lesion, cordotomy and sympathectomy, have only
be reported as useful anecdotally and should be
considered as a last resort in cases refractory to all
other treatments.
Oral opioids can occasionally be helpful and should
be tried before contemplating a more invasive
treatment modality. Oral NSAIDs and antiviral
agents have no place in the treatment of established
PHN.
Early treatment with an antiviral agent during
the acute zoster attack has shown some promise
in the reduction of incidence of the subsequent
development of PHN, although further large-scale
studies are required to confirm preliminary findings.
Corticosteroids and sympathetic blocks during the
acute phase cannot prevent PHN. Prophylactic
tricyclic antidepressants such as amitriptyline
during the acute stage have been reported to reduce
the incidence of PHN.
Phantom pain
Phantom pain is defined as pain referred to a
surgically removed limb or portion thereof. In
fact, phantom pain can occur in body parts other
than the limbs. For instance, phantom pain has
been reported following mastectomy [44], or after
tooth extraction [6]. Phantom sensation occurs
almost invariably after amputation, and phantom
pain, being a special form of phantom sensation,
is a grossly underestimated problem. is is
related in part to the reluctance of many patients
to report phantom pain for fear of being labelled
as malingering or insane. e true incidence of
phantom pain lies somewhere between 30–75%
of amputees. e incidence is higher in patients
who experienced pain in the amputated part before
amputation [39], in proximal amputations and in
older patients. It is interesting that phantom pain
has never been reported in children less than five
years of age. ere is no difference in the incidence
of phantom pain after amputation for traumatic or
non-traumatic causes [36].
Phantom pain can occur any time after an
amputation. It may commence at the time of
amputation, or develop years later. Phantom pain
usually improves with time. However, the duration
of symptoms in a lot of amputees is adequate to cause
significant social and employment disturbances.
Clinically, the pain is continuous with exacerbations.
e major differential diagnosis is with stump
pain, which is due to a neuroma at the stump. e
differentiating features are summarised in table
15.03.
Phantom pain is a type of neuropathic pain often
called “deafferentation pain”. Deafferentation
implies the pain is initiated by injury to nerves,
either peripheral or central. e pathophysiology of
phantom pain is poorly understood. Following the
Table 15.03 Comparison of stump pain and phantom pain
Stump pain Phantom pain
Pain location
At the amputation stump In the non-existent (phantom) body part
Onset
Usually delayed Highly variable
Pain character
Aching, stabbing, electrical.
Aggravated by tapping over stump
Cramping, burning, sometimes shock-like. Not
aggravated by tapping
Pathophysiology
Neuroma at stump Central nervous system mechanisms (see text)
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Neuropathic Pain 243
initiating injury (amputation), central sensitisation
develops in the spinal cord as well as the brain. Most
people believe the NMDA receptors are involved,
which result in some form of “pain memory”, or
plasticity in the spinal cord and brain [32]. is
pain memory is re-experienced later on, probably
accentuated by the lack of actual afferent input
after amputation, giving rise to persistent phantom
sensation and pain.
Treatment of phantom pain should start with
oral medications. A combination of tricyclic
antidepressants such as amitriptyline and
anticonvulsants such as gabapentin [8] or sodium
valproate is effective in a number of patients. Non-
steroidal anti-inflammatory drugs can be added
if relief is not satisfactory. A special treatment for
phantom pain, especially pain of recent onset, is
intravenous calcitonin infusion (200 IU salmon
calcitonin over 30 minutes). is treatment can
be highly effective in some patients, with little
side effect [35]. A single infusion is often all that is
required to produce long-lasting relief. If needed,
the treatment can be repeated after a few months.
It should be tried in all patients with less than a 1
month’s history of phantom pain. Intranasal and
subcutaneous administrations seem to be equally
effective.
e next treatment options for patients who fail
to respond to oral treatment or calcitonin are oral
opioids, subcutaneous ketamine and intrathecal
or epidural opioids. Somatic nerve blocks with
local anaesthetics are seldom effective and may
sometimes paradoxically increase the pain [46].
Sympathetic blocks such as stellate ganglion or
lumbar sympathetic block, spinal cord stimulation
and deep brain stimulation, cordotomy or dorsal
entry zone lesion have all been tried and success
claimed anecdotally. However, the value of these
procedures in managing phantom pain remains to
be established.
Careful differentiation of true phantom pain from
stump pain is the most important first step in the
management of phantom pain. Besides the specific
treatment, a well-fitting prosthesis and effective
physiotherapy are also extremely important. ese
may not have direct analgesic effect, but are central
to translating the effort of the pain physician into
improved function, and can greatly enhance the
general well-being of the patient.
Complex regional pain
syndrome
Complex regional pain syndrome (CRPS) is a new
term introduced in the 1994 IASP pain terminology
update. ere are two types of CRPS, CRPS I
and CRPS II. e features common to both are
persistent neuropathic pain in some part of the
body (therefore “regional”), usually a limb, with
some associated trophic changes in the affected
area, such as skin atrophy. e signs and symptoms
are usually more severe in the more distal part
of the affected area. e signs and symptoms are
also much exaggerated in magnitude and duration
compared with what might be expected from the
inciting event. Significant impairment of motor
function is common [77].
A closely related term is sympathetically maintained
pain (SMP). is refers to pain that is maintained
by sympathetic efferent innervation or circulating
catecholamines. Sympathetically maintained pain
is a feature of several types of pain condition and is
not an essential requirement of any one condition.
In particular, whereas SMP is frequently present
in patients with CRPS, some patients with CRPS
do not show features of SMP. Another point worth
noting is that the presence of SMP does not exclude
the presence of sympathetically independent pain.
On the contrary, the two conditions can coexist in
one patient.
Complex regional pain syndrome I (CRPS I)
Previously called reflex sympathetic dystrophy,
CRPS I is a syndrome that usually develops after an
initiating noxious event. e pain is not limited to
the distribution of a single peripheral nerve and is
apparently disproportionate to the inciting event.
e term reflex sympathetic dystrophy has been
dropped from the description of this condition
because it is observed that not all CRPS I patients
have SMP and not all show dystrophy.
As with many other chronic pain conditions,
CRPS I is probably an under-reported condition.
Orthopaedic injury to an extremity is the most
common predisposing factor. e severity of the
injury does not seem to affect the incidence of
subsequent development of CRPS I or otherwise.
Colles’ fracture, which traditionally has been
associated with reflex sympathetic dystrophy,
probably has an incidence of CRPS I of 5–30%.
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244 Kwok Fu Jacobus NG
Surgical trauma such as arthroscopy can also
precipitate CRPS I [57]. Women are about three
times more likely to be affected compared with men,
and the peak incidence age is 40–50 years [84].
e condition has also been reported in children.
In some cases, a precipitating injury may never be
identified. Whether CRPS I can develop without
a precipitating injury at all is only of academic
interest, as almost all pain physicians will agree a
“very trivial” injury can precipitate CRPS I. Some
have even suggested that CRPS I can be precipitated
by psychological stress itself, without any physical
injury. It is likely that cases that have been reported
as precipitated by stress alone involved some trivial
injury which has been overlooked or forgotten by
the patient.
Complex regional pain syndrome II (CRPS II)
Previously called causalgia, CRPS II is identical
to CRPS I except for the initial inciting event.
Whereas CRPS I develops after a noxious event
which is not a nerve injury, CRPS II refers to the
same problem developing after partial injury of a
nerve or one of its major branches. It should be
noted that although CRPS II starts off from a
nerve injury, the ultimate affected area need not be
confined to the distribution of a peripheral nerve,
or a dermatome.
e nerves most commonly involved in the
development of CRPS II are the median, the sciatic,
the tibial and the ulnar nerves. e commonest
mode of injury is stretching of the nerve, for example
by a high-speed missile injury. Interruption of the
nerve is not required. e incidence of CRPS II
after a classic injury is around 1–5% [61].
e natural course, clinical features, pathophysiology
and treatment for CRPS I and II are very similar
and will be discussed together below.
Although some cases of CRPS can be self-limiting,
most patients with CRPS suffer long-lasting pain.
Some 25–40% of patients with CRPS still have
pain at 10-year follow-up [23]. Some patients have
repeated remissions and relapses, and some unlucky
patients have progressive increase in pain and
disability. is is a disabling condition and loss of
function and the social disability are as significant
a problem as the pain itself to many sufferers. Also,
CRPS is notoriously associated with psychological
problems, both in the pathogenesis and in the
maintenance of the condition.
e progression of CRPS has traditionally been
divided into three stages. e initial stage is called
the acute stage, followed by the dystrophic stage
and finally the atrophic stage. Whereas these well-
defined stages are present and very valuable in
terms of diagnosis and prognosis in a small number
of patients with CRPS, many patients may show
only incomplete or mixed characteristics of these
stages.
Complex regional pain syndrome is a clinical
diagnosis. ere are four diagnostic criteria for
CRPS I and three for CRPS II (Table 15.04).
History and careful examination should suffice
to establish or refute a diagnosis of CRPS in
Table 15.04 The IASP diagnostic criteria for CRPS
[52]
CRPS I CRPS II
1. The presence of an
initiating noxious
event, or a cause of
immobilisation
1. Continuing pain,
allodynia, or
hyperalgesia after
a nerve injury, not
necessarily limited
to the distribution of
the injured nerve
2. Continuing pain,
allodynia, or
hyperalgesia which
is disproportionate
to any inciting event
2. Evidence at
sometime of
oedema, changes
in skin blood
flow, or abnormal
sudomotor activity
in the region of pain
3. Evidence at
sometime of
oedema, changes
in skin blood
flow, or abnormal
sudomotor activity
in the region of pain
3. The diagnosis
is excluded by
the existence of
conditions that
would otherwise
account for the
degree of pain and
dysfunction
4. The diagnosis
is excluded by
the existence of
conditions that
would otherwise
account for the
degree of pain and
dysfunction
Criteria 2–4 must be
satisfied
All 3 criteria must be
satisfied
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Neuropathic Pain 245
most circumstances. Besides establishing the
necessary criteria, the clinical history should also
be directed at revealing problems with the patient’s
personality or social environment. Exacerbation of
pain by exercise is also a useful symptom to note.
In cases where the symptoms and clinical signs
are equivocal, tests can be ordered to help in the
diagnosis. Autonomic changes can be established
by demonstration of asymmetric skin temperatures
(>1oC, demonstrated on at least two separate
occasions) [64], or by testing of sudomotor
function, both at rest and evoked. Trophic changes
can be demonstrated on plain radiography as patchy
demineralisation, or abnormal radionuclide uptake
on bone scintigraphy. A three-phase Technetium
(99mTc) scanning is the most commonly employed
bone scintigraphy technique. e delayed three-
phase scans showing diffuse regional uptake are
especially useful, having over 80% sensitivity and
specificity for CRPS [33].
e major differential diagnoses for CRPS are listed
in Table 15.05 [52].
A trial sympathetic block only serves to test whether
the condition is sympathetically maintained and is
not necessary in the diagnosis of CRPS. However,
these blocks can provide useful information
about the probable efficacy of certain treatment
modalities, which will be discussed below.
e pathophysiology of CRPS is not clearly
understood. ere is a strong general suspicion
that CRPS involves some pathophysiological
process in the central nervous system, with or
without concomitant changes in the peripheral
nervous system [29]. e central process involved
is most likely central sensitisation via NMDA and
tachykinin-mediated actions on spinal neurons
[93, 94]. e initial stimulus for and maintenance
of this sensitisation can result from ongoing C-
afferent input, augmented by postganglionic
sympathetic neurons in the case of sympathetically
maintained pain. is result includes threshold
reduction, increased responsiveness, recruitment
of novel inputs and widening of receptive fields
in dorsal horn neurons [14, 74, 91]. In addition
to these neurological processes, CRPS also seems
to have a significant inflammatory element in its
pathogenesis. For instance, there is accumulation
of immunoglobulins and changes in oxygen
extraction in the affected area [31] which is
compatible with an inflammatory process. e
sympathetic element in those instances of CRPS
which are sympathetically maintained are generally
believed to be related to up-regulation of alpha-
1-receptors peripherally. Sympathetic-nociceptor
ephapses and increased activity in nociceptive
afferents travelling with sympathetic efferents may
also contribute.
Complex regional pain syndrome is a difficult
condition to treat. Reasons for this difficulty are
threefold. First, the pathophysiological processes of
CRPS are highly complicated involving multiple
mechanisms and poorly understood. Second, there
is a paucity of well-designed, large-scale clinical
trials in this area. Many treatment modalities are
based on a trial-and-error basis or on small-scale
studies or anecdotal reports. ird, there is usually
a prominent psychological and socioeconomical
element in the patient’s problem.
It should be emphasised that the objective of
management of CRPS, as in the case of many other
chronic pain conditions, is not just analgesia. Early
exploration of psychological factors in the disease
process, minimising the “sick role”, reducing anxiety
in general, identification of “secondary gains”, and
counselling family members, close friends and
relatives are all integral aspects of the treatment
programme. Rehabilitation and restoration of
function is as important as analgesia itself, and the
two will usually be complimentary to each other.
e use of invasive or surgical treatment, such
as neurodestructive procedures, implantation of
neurostimulatory devices, or amputation of body
parts, should be reduced to a minimum. None of
these treatments has been shown to offer any benefit;
moreover, they are likely to be counterproductive in
terms of the psychological rehabilitation of CRPS
patients.
Early physical therapy does have an important
role in the management of CRPS. Physiotherapy
Table 15.05 Differential diagnoses for CRPS
1. CRPS (I from II or vice versa)
2. Unrecognised local pathology — fracture,
sprain, strain
3. Traumatic vasospasm
4. Cellulitis
5. Raynaud’s disease
6. Thromboangiitis obliterans
7. Paget’s disease
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246 Kwok Fu Jacobus NG
directed at improving mobilisation, such as exercise
programmes, stress-loading, passive movement and
pool therapy, can all be helpful. ese programmes
will be significantly facilitated by provision of
effective analgesia. Positive pressure treatments for
oedema, lymphatic drainage and cooling are other
treatment options [28]. Transcutaneous electrical
nerve stimulation is non-invasive, simple to use
and inexpensive, and should be offered for a trial
in all patients, especially children. It is sometimes
highly effective. However, some patient’s pain can
occasionally be aggravated by TENS.
In addition to psychological and physical
therapies, the first-line treatment in CRPS is still
pharmacological. Unfortunately, a recent review
of clinical trials showed that oral corticosteroid is
the only treatment to have demonstrated analgesia
consistently [41]. e usual starting dose is
prednisolone 30–60 mg per day orally, gradually
tapering off over weeks [9, 12]. Corticosteroids
should be used with caution in children. e
inflammatory response certainly plays an important
role in the pathogenesis of CRPS, as other anti-
inflammatory treatments have recently also been
found to be useful. is includes topical treatment
with the free radical scavenger dimethylsulfoxide
[63, 95], and the systemic administration of COX-
2 inhibitors [25].
Intranasal and subcutaneous calcitonin, initially
intended to treat the osteoporotic changes of
CRPS, have also be reported to provide some
analgesia [27], but there are also reports of
contradictory findings. Bisphosphonates, such as
alendronate or pamidronate, have recently been
found to be useful in CRPS. Bisphosphonates
may be administered orally over 6 to 8 weeks
[48] or by daily intravenous administration for
a few days [1, 83]. e mechanism by which
bisphosphonates produce pain relief in CRPS
remains unclear.
Other drugs such as antidepressants, anticonvulsants,
NSAIDs, nifedipine and clonidine can only be
recommended on a trial-and-error basis, and their
benefit must be carefully weighed against their
numerous side effects. Should a combination of
physical, psychological and oral drug therapies
prove unsatisfactory, sympathetic blockade
and other nerve blocks may be tried. e use of
opioids is highly controversial and the response
is also unpredictable. If patients do respond, the
only sensible role of opioid may be in providing
analgesia cover for the initiation of a mobilisation
physiotherapy programme. Long-term opioid
treatment is not appropriate.
Sympathetic blockade can be performed in three
ways. First, a sympathetic ganglion can be blocked,
such as the stellate ganglion for upper limb
involvement and a lumbar sympathetic block for
lower limb involvement. Second, an intravenous
regional block (IVRB) can be performed using
various drugs, including guanethidine, bretylium
and reserpine, together with local anaesthetic.
ird, a systemic block can be tried with oral
phenoxybenzamine or intravenous phentolamine
(Table 15.06). As discussed above, not all CRPSs
are sympathetically maintained, so the response to
a sympathetic block is consequently highly variable.
In fact, the response to a sympathetic block is the
method used to evaluate the presence or absence
of a sympathetic element in a patient with CRPS.
If patients are found to respond favourably, then
usually a series of blocks will be performed with
some lasting benefit.
Epidural local anaesthetic infusion can sometimes
significantly reduce the pain in CRPS. is
technique can be used for in-patients to provide a
more favourable condition for physical therapies.
Epidural opioids and clonidine may or may not
be effective. Implantation of pumps is usually not
warranted.
In patients who do not respond to oral medications
and intravenous regional treatment, another
Table 15.06 Intravenous regional block and
systemic sympathetic block in CRPS [41]
Technique Drug and dose recommended
IVRB Notes:
1. Add drug to 30–50 ml 0.5%
lignocaine
2. Use smaller dose for upper limb,
larger dose for lower limb
Guanethidine 10–30 mg
Bretylium 1–1.5 mg/kg
Reserpine 1.25 mg
Systemic
block
Phenoxybenzamine 40–120 mg/day
oral Phentolamine 25–35 mg IV over
30 minutes
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Neuropathic Pain 247
option is to perform spinal cord stimulation[80].
e details of this technique, its advantages and
limitations are discussed in more detail in Chapter
29.
Central pain
Central pain is defined as regional pain caused by a
primary lesion or dysfunction in the central nervous
system, usually associated with abnormal sensibility
to temperature and to noxious stimulation.
e distribution of pain in a patient with central
pain correlates anatomically with the location of
the lesion in the brain or spinal cord. erefore,
the region of pain may be all or most of one side
of the body, all parts of the body caudal to a level,
or both extremities on one side. It may also be
restricted to just one extremity or one particular
part of the body. Sometimes the distribution
suggests the diagnosis, for example a cheiro-oral
distribution (perioral region and ipsilateral hand) is
characteristic of thalamic pain. Central pain is only
a collective term. ere are various pain syndromes
named after either the location of the lesion or
the underlying disease that belong to the category
of central pain. Some examples include thalamic
pain, post-stroke pain and pain due to multiple
sclerosis.
Central pain is not an uncommon problem. e
incidence is around 10–30% after spinal cord
injury and 25–80% in patients with multiple
sclerosis. e many causes of central pain are listed
in Table 15.07.
In most patients with central pain, the pain will
persist unless the underlying lesion is corrected. e
pain is usually a great physical and psychological
burden to patients, frequently rendering them
physically and socially handicapped.
Central pain is characterised by a complex quality
of pain, usually involving a description such as
burning or lancinating. ere is frequently allodynia
and uncomfortable paraesthesias. Hyperpathia
is common in thalamic pain. e pain is usually
spontaneous and continuous. It can be exacerbated
by touch, heat, cold or movement. e pain can
also be augmented by startling stimuli (e.g. sudden
sound or light), by visceral activity (e.g. micturition)
or by anxiety and emotional arousal. Associated
neurological symptoms and signs are common.
ese may include hemiparesis, paraparesis and
sensory impairment [45]. e diagnosis of central
pain is further supported by the presence of a
history of neurological disorder or evidence of such
on computed tomography or magnetic resonance
imaging. e major differential diagnoses include
nociceptive pain, peripheral neuropathic pain and
psychiatric cause of pain.
Central pain is basically a “deafferentation pain”.
Damage to the spinothalamocortical pathway is
the common feature in any central pain syndrome.
is damage may induce painful processes in
the central nervous system and disinhibition of
nociceptive neurons in the thalamus may be an
important process.
Transcutaneous electrical nerve stimulation may
be useful in some patients with central pain.
As with cases of CRPS, TENS may aggravate
the pain in some patients. Most patients with
central pain require some pharmacological
treatment. Antidepressants such as amitriptyline,
nortriptyline and clomipramine are the first-line
treatment. Anticonvulsants such as gabapentin,
lamotrigine or carbamazepine can be tried next
if antidepressants provide inadequate relief [45,
55, 62, 85]. ere are anecdotal reports of a
satisfactory response to mexiletine, propranolol,
anticholinesterase inhibitors, chlorpromazine, 5-
hydroxytryptophan and even a brief intravenous
infusion of naloxone. ese may be tried if the
Table 15.07 Causes of central pain
Systemic disease
Multiple sclerosis
Diabetes mellitus
AIDS
Spinal cord lesions
Trauma including surgery and irradiation
Vascular lesions
Syringomyelia
Neoplasms
Myelitis
Subacute combined degeneration
Cerebral and thalamic lesions
Stroke
Trauma including surgery and irradiation
Vascular lesion — arteriovenous malformations
and aneurysms
Neoplasms — primary and metastatic
Brain abscess
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248 Kwok Fu Jacobus NG
pain has proved refractory. Some patients will
respond to opioids, at least partially. e decision
to use opioids should be made after careful
evaluation of the patient’s underlying disorder
and psychological status, and on the merits of the
individual patient.
More invasive procedures are sometimes used to
control refractory central pain. ese include dorsal
root entry zone lesion in patients with spinal cord
pain and deep brain stimulation. ese techniques
are discussed in more detail in Chapter 30.
Summary
• Neuropathic pain is defined as “Pain initiated
or caused by a primary lesion or dysfunction
in the nervous system”
• Common symptoms in patients with
neuropathic pain include shooting pain,
burning pain, lancinating pain, allodynia and
hyperalgesia; the pain can be spontaneous or
evoked
• Neuropathic pain is commonly found in
chronic pain patients
• e pathophysiological mechanisms of
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