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Case Studies in Pain Management

Edited by Alan David Kaye, Rinoo V. Shah
Book DOI: http://dx.doi.org/10.1017/CBO9781107281950
Online ISBN: 9781107281950
Paperback ISBN: 9781107682894

Chapter
Chapter 7 - Complex regional pain syndrome pp. 46-51
Chapter DOI: http://dx.doi.org/10.1017/CBO9781107281950.008
Cambridge University Press

Section 1
Chapter

Neurological Disorders

Complex regional pain syndrome

Gaurav Jain and Nashaat N. Rizk

Case study
A 50-year-old woman sustained an injury to her right
wrist after a computer fell on it. A few weeks later she
had pain and swelling in her right wrist. All wrist
movements were painful. Due to the possibility of
tendon injury, a plastic surgeon operated on her wrist
and found no abnormalities. After surgery, her hand
was swollen and pain worsened. It was mostly aching
and burning, but sometimes sharp in nature. Gradually, she was unable to use her right hand due to pain,
swelling, discomfort, tightness, and weakness. Gradually, she started to notice that the right hand felt
colder and looked paler than the other hand. She had
poor nail growth and the skin on her affected hand
became dry. She was crippled in her personal and
occupational life due to the above condition.

1. What are the differential diagnoses

in this case?
 Cellulitis
 Lymphedema
 Soft tissue or bone injury, including occult or
stress fracture
 Compartment syndrome
 Arthritis or arthrosis
 Tenosynovitis
 Upper or lower limb venous thrombosis
 Arterial insufficiency such as thromboangiitis
obliterans or severe atherosclerosis
 Scleroderma
 Plexitis, peripheral neuropathy
 Erythromelalgia

2. What is complex regional pain

syndrome?
Complex regional pain syndrome (CRPS) is a
chronic regional (not in a specific nerve territory or
dermatome) pain syndrome that occurs most often
in an extremity in association with abnormal autonomic nervous system activity and trophic changes.
The pain is seemingly disproportionate in time or
degree to the usual course of any known trauma or
other lesion. The disorder has both nociceptive and
neuropathic features and is characterized by disabling persistent pain, hyperalgesia or allodynia, swelling, vasomotor instability, sudomotor abnormality,
and impairment of motor function. In many cases,
the syndrome is preceded by an inciting noxious
event, surgery, trauma, or immobilization, while in
some cases (9%) there is no precipitating trauma
at all. However, the condition is not related to
trauma severity. The syndrome shows variable progression over time. Transient features of CRPS are
much more common than most clinicians realize,
occurring in up to 25% of minor limb injuries.
Approximately 15% of sufferers will have unrelenting
pain and physical impairment up to 5 years after
CRPS onset, although more patients will have a
lesser degree of ongoing pain and dysfunction
impacting their ability to work and function normally. The incidence per person-years at risk of
CRPS based on the results of two epidemiologic
studies ranged from 5.46 to 26.6/100000 personyears at risk. It is commoner in females than males,
at a ratio of 23:1, and frequently occurs in the 5th
7th decade of life.

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press.
Cambridge University Press 2015.

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Chapter 7: Complex regional pain syndrome

Table 7.1. The 2007 Budapest Consensus Dignostic Criteria for CRPS*

Category

Symptom

Sign (evidence needed on exam)

Sensory

Hyperesthesia and/or allodynia

Hyperalgesia (to pinprick) and/or allodynia (to light

touch and/or temperature sensation and/or deep
somatic pressure and/or joint movement)

Vasomotor

Temperature asymmetry and/or skin color changes

and/or skin color asymmetry

Temperature asymmetry (> 1C) and/or skin color

changes and/or asymmetry

Sudomotor/
edema

Edema and/or sweating changes and/or sweating

asymmetry

Edema and/or sweating changes and/or sweating

asymmetry

Motor/
trophic

Decreased range of motion and/or motor

dysfunction (weakness, tremor, dystonia) and/or
trophic changes (hair, nail, skin)

Decreased range of motion and/or motor

dysfunction (weakness, tremor, dystonia) and/or
trophic changes (hair, nail, skin)

* One symptom in at least three categories and one sign in at least two categories are required for diagnosis.

3. What are the classification and

diagnostic criteria of CRPS?
CRPS is classified into two types based on the absence
(type I) or presence (type II) of a definable nerve
injury. In 1998, the International Association for the
Study of Pain (IASP) established the following four
criteria that must be present for a clinical diagnosis of
CRPS to be made:
1. Preceding noxious event without (CRPS I) or with
obvious nerve lesion (CRPS II).
2. Spontaneous pain or hyperalgesia-hyperesthesia
not limited to a single nerve territory and
disproportionate to the inciting event.
3. Edema, skin blood flow (temperature), or
sudomotor abnormalities, motor symptoms, or
trophic changes present in the affected limb, in
particular at distal sites.
4. Other diagnoses are excluded.
Although the IASP diagnostic criteria had a high
sensitivity, their specificity was only around 40%. In
2007, the Budapest Consensus refined the diagnostic
criteria to include stricter conditions for clinical diagnosis, which increased the specificity to about 70%
while maintaining high sensitivity. The criteria were
as follows:
1. Continuing pain disproportionate to any
inciting event
2. Must report at least one symptom in three of the
four categories listed in Table 7.1

3. Must display at least one sign at time of evaluation

in two or more of the categories listed in Table 7.1
4. No other diagnosis better explains the signs and
symptoms (see Table 7.1)
Schwartzman et al divided CRPS into three clinical
stages, which are useful descriptively. The syndrome
may not always follow this stepwise evolution. The
stages of CRPS are described as follows:
i. Stage 1: severe pain; pitting edema; redness;
warmth; increased hair and nail growth;
hyperhidrosis may begin; osteoporosis
may begin.
ii. Stage 2: continued pain; brawny edema;
periarticular thickening; cyanosis or pallor; livedo
reticularis; coolness; hyperhidrosis; increased
osteoporosis; ridged nails.
iii. Stage 3: pallor; dry, cool skin; atrophic soft
tissue (dystrophy); contracture; extensive
osteoporosis.

4. How does one make the diagnosis

of CRPS?
CPRS is primarily a clinical diagnosis The pathophysiology of CRPS is poorly understood. Based on current literature, several hypothesized mechanisms
appear to play roles: autonomic dysfunction, neurogenic inflammation, and neuroplastic changes within
the central nervous system (central/peripheral sensitization and progressive small-fiber degeneration).

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Chapter 7: Complex regional pain syndrome

Currently no diagnostic test is considered a gold

standard and no objective test is specific for CRPS.
However, several diagnostic studies may be helpful in
its evaluation and to rule out other pathologic
processes.
Autonomic function can be assessed by following
tests: infrared thermometry and thermography, quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), and laser Doppler
flowmetry. The skin temperature can be measured by
Doppler flowmeter and infrared thermography; cutaneous blood flow can be measured by vital capillaroscopy (the affected extremity may demonstrate higher
perfusion); sweat output can be assessed by quantitative
sudomotor axon reflex testing; and coexisting nerve
injury and muscle fiber loss can be quantified by electromyography and nerve conduction studies. The limitations of these tests are non-specific to this condition
and most require special equipment and setup that make
clinical applications less viable. Imaging is useful to
exclude other diagnoses.
Plain films are usually normal except in extreme
cases, in which demineralization can occur (Sudecks
atrophy). Trophic changes can be assessed by threephase bone scintigraphy, which detects pathologic
delayed uptake in the distal bones such as the metacarpophalangeal or metacarpal bones. The sensitivity
and specificity of three-phase bone scintigraphy are
variable. Although an abnormal bone scan finding can
confirm the clinical diagnosis of CRPS, the condition
cannot be ruled out by a normal study. Magnetic resonance imaging may demonstrate marrow edema, soft
tissue swelling, and joint effusion. Although clinically
unavailable, central nervous system functional imaging
studies may provide clues to reorganization in central
somatosensory and motor networks, which lead to an
altered central processing of tactile and nociceptive
stimuli, as well as to an altered cerebral organization
of movement.

5. What is the treatment approach

for CRPS?
Prompt diagnosis and early treatment is the cornerstone in management. It helps to avoid secondary
physical problems associated with disuse of the
affected limb and the psychologic consequences of
living with undiagnosed chronic pain. Early referral
to physiotherapy and encouraging gentle movement as

early as possible may potentially prevent progression

of symptoms. Except in mild cases, patients with
CRPS are generally best managed in specialist pain
management or rehabilitation programs. An integrated and interdisciplinary pain rehabilitation treatment approach that includes the following four
components is required:
a. Patient information and education
b. Pain relief with medications and procedures
c. Physical and vocational rehabilitation
d. Psychologic interventions (pain-coping skills,
biofeedback, relaxation training, and cognitive
behavior therapy)
Treatment with medications and procedures can be
individualized according to the symptoms, signs, and
degree of severity. Tricyclic antidepressants are traditional choices in neuropathic pain disorders with
good evidence to support their use for neuropathic
pain. Antiepileptic agents are some of the best-studied
agents for neuropathic pain, and strong evidence
demonstrates their effectiveness. Non-steroidal antiinflammatory drugs may be effective in the acute
phase with symptoms of swelling, erythema, or
warmth. Oral corticosteroid agents can be particularly
effective early in the disease when significant inflammation is present, and their use is substantially supported by randomized controlled clinical trials.
A short course of steroids in the acute stage of the
disease may be indicated. The lidocaine patch is used
topically to deliver medication locally to the area of
allodynia. Because of the suspected role of increased
sympathetic nervous system activity in CRPS, alphaadrenergic antagonists such as phenoxybenzamine
and phentolamine have also been used and may be
beneficial in cases of sympathetically maintained pain.
Opioids may be useful in the acute stages of CRPS for
pain control. However, their use in chronic pain conditions and conditions with neuropathic features
remains controversial. Methadone may be a choice
in cases of severe neuropathic pain because of its
NMDA receptor antagonist activity. Bisphosphonates
have been tested in randomized controlled trials with
some demonstrated efficacy, with the assumption that
antinociceptive effect is primarily due to their capacity to inactivate osteoclasts and inhibit prostaglandin E2, proteolytic enzymes, and lactic acid.
Calcitonin is another recent addition to the CRPS
drug therapy armamentarium. However, results of
randomized trials have been equivocal.

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Chapter 7: Complex regional pain syndrome

6. What interventional methods are

available to treat CRPS?
Local anesthetic sympathetic blockade is the conventional and most common early intervention. However, patients can be divided by those with
sympathetically maintained pain and those with sympathetically independent pain based on positive or
negative response to selective sympathetic blockade
or blockade of the alpha-adrenergic receptors. Stellate
ganglion blocks for upper limb and lumbar chain
blocks for lower limb symptoms can be offered. Alternatively, intrapleural infusion of local anesthetic can
be used to block the sympathetic chain from T1 to L2.

Bier block procedures, involving the intravenous

infusion of pharmacologic substances into a limb
after gravitational drainage of the venous bed, may
also be used. Depending on the substance infused, this
can accomplish regional sympathetic blockade with
guanethidine, sensorimotor blockade with lidocaine,
or a combination of the two. For those patients with
sympathetically independent pain, regional sensorimotor blockade with lidocaine should be the early
intervention of choice. Such procedures have the possibility of achieving rapid and effective pain relief,
allowing more timely progression in rehabilitation.
In addition to interventional pain control procedures, which should be used aggressively early in the
Figure 7.1. Lumbar sympathetic block.
From personal files of Rinoo V. Shah, MD,
MBA.

Figure 7.2. Stellate ganglion block.

From personal files of Rinoo V. Shah, MD,
MBA.

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Chapter 7: Complex regional pain syndrome

Figure 7.3. Spinal

cord stimulation.
From personal files
of Rinoo V. Shah,
MD, MBA.

Figure 7.5. Same patient as Figure 7.4: cervical spinal cord

stimulation midline (dorsal columns) and dorsal root/entry zone
stimulation. From personal files of Rinoo V. Shah, MD, MBA.

Figure
7.4. Cervical spinal
cord stimulation
midline/dorsal
columns. From
personal files of
Rinoo V. Shah, MD,
MBA.

disease course, spinal cord stimulation (SCS) can be a

beneficial treatment modality for those who do not
have a satisfactory response to the above treatment in
1216 weeks. SCS has been shown to be effective for
treatment of both CRPS I and CRPS II when other less
invasive treatment strategies have failed. Neuromodulation may act to restore normal gamma-aminobutyric
acid levels in the dorsal horn and affect release of
adenosine, thus reducing neuropathic pain. SCS has
proven effective in supporting functional restoration in
the affected limb. Peripheral nerve stimulation uses a
similar technique to SCS. However, due to a new
modality, available data is limited. A spinal cord stimulator lead can sometimes be placed in the dorsolateral
epidural space to target the dorsal roots or dorsal root
entry zone.
Patients who have a good response to sympathetic
blocks can be offered sympathetic denervation through
radiofrequency ablation or surgical sympathectomy.
However, the quality of evidence for these treatments
is poor and several complications can occur, which
include postsympathectomy sympathalgia, compensatory hyperhidrosis, Horners syndrome, infection, and
spinal cord injury.

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Chapter 7: Complex regional pain syndrome

Sometimes CRPS may spread to the contralateral

limb or to involve a different region of the body. Surgeons operating on patients with resolved or dormant
CRPS must be aware of reactivation and spread of this
disease, even if the surgery is remote to the original
CRPS involved limb. If recurrence and spread occur,
blocks and infusions targeting the sympathetically independent and maintained pain generators should be
pursued, according to Shah and Day.[15]

7. What is the course of CRPS?

The outcome of CRPS varies from person to person.
Younger patients, especially children and teenagers,
tend to have good recovery. Occasionally patients are
left with unremitting pain and crippling, irreversible

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