Chapter 50 Complex Regional Pain Syndrome

Question 1

Complex regional pain syndrome (CRPS) Types I and II
(formerly known as reflex sympathetic dystrophy [RSD]
and causalgia, respectively)

Answer 1

CRPS describes an array of painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is
seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The pain is regional (not in a specific nerve territory or dermatome) and usually has a distal
predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings. The syndrome shows variable progression
over time.

Question 2

causalgia

Answer 2

a constant burning pain

Question 3

The radiographic changes started

as a

Answer 3

“patchy osteoporosis of the small bones of the hands

or feet and the distal metaphysis of the forearm or tibial bones,”

Question 4

term complex regional pain

syndrome was therefore considered broad enough to allow the inclusion of patients who

Answer 4

may show varying levels of sympathetic nervous system involvement in maintaining pain
through the course of the disease process, hence the term sympathetically mediated pain (SMP) or sympathetically independent pain (SIP)

Question 5

CRPS commonly occurs

among

Answer 5

younger females and often results from workrelated

injuries or surgery

Question 6

CRPS is associated with

Answer 6

sleep disturbance, functional impairment, and suicidal ideation

Question 7

CRPS Type I and Type II differ only by

Answer 7

the presence

(Type II) or absence (Type I) of evidence of nerve injury.

Question 8

hallmark of the condition

Answer 8

Pain is the hallmark of the condition, and commonly manifests as spontaneous pain, with hyperalgesia and allodynia.

Question 9

Associated signs include

Answer 9

vasomotor and, sudomotor active
disturbances and passive movement disorders in addition to
trophic changes

Question 10

CRPS Type I and Type II difference

Answer 10

CRPS Type II develops after defined nerve injury, whereas CRPS Type I develops following minor or major injuries with little or no obvious damage to the nerves
in the involved extremity.

Question 11

Peripheral sensitization

Answer 11

resulting from the persistent nociceptive
afferent activity as a result of the initial tissue
trauma is thought to occur

Question 12

Following local injury, the

primary afferent fibers in the traumatized area release

Answer 12

neuropeptides such as bradykinin and substance P, which result in increased firing of nociceptors to noxious stimuli and reduced firing threshold to mechanical and thermal stimuli; this may account for the hyperalgesia and allodynia pathognomonic of CRPS

Question 13

CENTRAL SENSITIZATION

Answer 13

Persistent nociceptive input associated with nerve injury from tissue trauma results in increased activity of nociceptive neurons in the spinal cord

Question 14

The central sensitization is mediated by

Answer 14

the induced release of neuropeptides such as bradykinin and substance P and the excitatory neurotransmitter glutamate
acting at the spinal N-methyl-d-aspartic acid receptors. This activity results in enhanced response to non-noxious
stimuli (allodynia) and noxious stimuli (hyperalgesia)

Question 15

There has been an indication of an interaction between
the sympathetic noradrenergic neurons in the periphery
and

Answer 15

the primary afferent neurons as part of the underlying mechanism of sympathetically maintained pain (SMP)
in patients with CRPS I.

Question 16

inflammatory
mechanisms may be responsible for the acute phase of
CRPS. This may occur either through the classic cascade
of release of pro-inflammatory cytokines

Answer 16

(interleukin-1b,
IL-2, IL-6, and tumor necrosis factor-a) from mast cells
and lymphocytes following tissue trauma, or secondary to
neurogenic inflammation causing the release of cytokines and neuropeptides (including substance P and calcitonin
gene–related peptide [CGRP])

Question 17

The neuropeptides can increase

Answer 17

tissue permeability and cause vasodilatation,

giving rise to the “warm CRPS” with edema

Question 18

Substance P and TNF-a can engender

Answer 18

osteoclastic activity, which may

contribute to the osteoporosis seen in CRPS

Question 19

Cortical reorganization in central somatosensory

and motor networks that may result in

Answer 19

altered central processing of tactile and nociceptive stimuli and cerebral organization of movement

Question 20

Diagnostic Criteria for CRPS I Reflex Sympathetic Dystrophy

Answer 20

1. The presence of an initiating
noxious event or a cause of
immobilization.
2. Continuing pain, allodynia, or
hyperalgesia with which the
pain is disproportionate to
any inciting event
3. Evidence at some time of
edema, changes in skin blood
flow, or abnormal sudomotor
activity in the region of the
pain.
4. This diagnosis is excluded by
the existence of conditions
that would otherwise account
for the degree of pain and
dysfunction.

Question 21

Diagnostic Criteria for CRPS II

Answer 21

1. The presence of continuing
pain, allodynia, or hyperalgesia
after a nerve injury, not
necessarily limited to the
distribution of the injured
nerve.
2. Evidence at some time of
edema, changes in skin blood
flow, or abnormal sudomotor
activity in the region of the
pain.
3. This diagnosis is excluded by
the existence of conditions
that would otherwise account
for the degree of pain and
dysfunction.

Question 22

key feature for both CRPS I and II

Answer 22

Pain

Question 23

With CRPS I, the pain and associated clinical signs and symptoms are typically

Answer 23

out of proportion to the inciting event. The pain is typically described as a burning deep-seated ache with a shooting quality and associated
allodynia or hyperalgesia

Question 24

To make the clinical diagnosis, the following criteria
must be met:

1. Continuing pain, which is disproportionate to any inciting
   event
2. Must report at least one symptom in three of the four following categories:

Answer 24

Sensory: Reports of hyperesthesia and/or allodynia
Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
Sudomotor/Edema: Evidence of edema and/or sweating changes
and/or sweating asymmetry
Motor/Trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

Question 25

To make the clinical diagnosis, the following criteria
must be met:

3. Must display at least one sign at time of evaluation in two or
   more of the following categories:

Answer 25

Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement)
Vasomotor: Evidence of temperature asymmetry (,1 °C) and/or skin color changes and/or asymmetry
Sudomotor/Edema: Evidence of edema and/or sweating changes
and/or sweating asymmetry
Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic
changes (hair, nail, skin)
4. There is no other diagnosis that better explains the signs and symptoms

Question 26

diagnostic criteria for CRPS Types I and II

Answer 26

based on the patient’s symptoms and signs.

Question 27

the IASP criteria suggest that patients should demonstrate

at least one symptom in each of the following categories:

Answer 27

sensory (hyperesthesia—increased sensitivity to sensory stimulation), vasomotor changes (temperature abnormalities,
including skin and color changes), sudomotor (fluid
retention—sweating abnormalities, edema), or motor (decreased
range of motion, weakness, tremor, dyskinesia, or neglect).In addition, signs in at least two of the four categories
indicated above should be noted on physical examination
of the patient.

Question 28

help differentiate from more common conditions that may mimic CRPS

Answer 28

A complete history and physical examination, including a through neurologic and vascular examination.

Question 29

Differential Diagnosis of CRPS

Answer 29

These include neurologic
conditions such as painful diabetic neuropathy, entrapment syndromes, discogenic disease, and thoracic outlet syndrome. In addition, vascular conditions should be considered
as possible causes in the differential diagnosis,
including deep venous thrombosis, cellulitis, vascular
insufficiency, lymphedema, and erythromelalgia.

Question 30

gold standard or objective test that is specific for CRPS

Answer 30

there is no diagnostic test

Question 31

QUANTITATIVE SENSORY TESTING

Answer 31

This involves the use of standardized psychophysical tests of thermal, thermal pain, and vibratory thresholds to assess the function of large fiber, myelinated small fiber, and unmyelinated small afferent fibers. Static and dynamic allodynia, allodynia associated with pinprick, hyperalgesia related to mechanical and heat stimuli, and temporal summation
(increased pain to repeated stimuli) may be abnormal
in patients with CRPS. Since no specific sensory pattern has been recognized with CRPS, assessment of the
signs and changes over time may provide a tool to track
response to treatment

Question 32

AUTONOMIC FUNCTION TESTS

Answer 32

This includes infrared thermometry and thermography,
quantitative sudomotor axon reflex test (QSART), thermoregulatory
sweat test (TST), and laser Doppler flowmetry.

Question 33

AUTONOMIC FUNCTION TESTS Limitation

Answer 33

The limitation of these tests is that most require special
equipment and a setup that make clinical applications less
viable.

Question 34

TEMPERATURE MEASUREMENT

Answer 34

The use of infrared thermometry and infrared thermography
to assess small skin temperature differences between
the sides of the body is reported to achieve sensitivity in
the order of 76% and specificity of 100%

Question 35

TEMPERATURE MEASUREMENT

this test clinically is dependent on

Answer 35

The utility of
maintaining controlled
thermoregulation during measurements. This is difficult
to achieve in most clinical situations. Therefore the measurements
should be made under conditions where thermoregulation
can be controlled to detect differences on
both side for enhanced accuracy of the test.

Question 36

TEMPERATURE MEASUREMENT
The direction
of the temperature difference is dependent on the duration
of the disease

Answer 36

Earlier in the disease process the affected limb may demonstrate elevated temperatures, while later on in the more chronic phase of the disease the affected
side may show lower temperature compared to the unaffected
side.

Question 37

VASCULAR ABNORMALITIES

Answer 37

In patient with the disease of less than 4 months’ duration,
vascular reflex responses may be assessed using Doppler
flowmetry. The affected extremity may demonstrate higher perfusion. In patients with duration of disease less than 15 months, skin perfusion was found to be either higher or lower, while in patients with a mean duration of 28 months
the affected limb demonstrated a lower perfusion and ultimately lower temperatures

Question 38

TROPHIC CHANGES

The value of a three-phase bone scintigraphy is in
the ability to

Answer 38

detect pathologic delayed uptake in the distal bones, such as metacarpophalangeal or metacarpal bones. Most of these changes have been reported to occur within the first year of the
disease

Question 39

TROPHIC CHANGES

X-ray bone densitometry has also been reported to have

Answer 39

a high sensitivity and specificity for CRPS.

Question 40

NSAIDs in the treatment of CRPS

Answer 40

NSAIDs can provide mild to moderate pain relief.

Question 41

Antidepressants

Answer 41

widely for the treatment of neuropathic pain. Norepinephrine and
serotonin blockers and selective norepinephrine blockers like amitriptyline and desipramine respectively, may exert
their influence by modulating the noradrenergic and serotonergic
descending pathways.

Question 42

Antidepressants usual dose

Answer 42

range for

these drugs is about 10 to 75 mg by mouth at night time

Question 43

Anticonvulsants

Answer 43

Gabapentin and pregabalin have been
shown to be effective in diabetic neuropathy and postherpetic
neuralgia (PHN). Studies in patients with CRPS
have also demonstrated analgesic effect of gabapentin

Question 44

carbamazepine

Answer 44

The Food and Drug Administration (FDA) has approved
carbamazepine for trigeminal neuralgia and may be considered
as a second-tier option for CRPS

Question 45

oxcarbazepine,

Answer 45

The analog of
carbamazepine, oxcarbazepine, which does not exhibit the
side effects of liver and bone marrow toxicity, may be used as an alternative drug

Question 46

Opioids

Answer 46

should therefore be used as part of a multimodal

pharmacologic treatment regimen, particularly if other single agents do not provide optimum analgesia

Question 47

Antidepressants and doses

Answer 47

Amitriptyline 10–75 mg/day qd at night
Nortriptyline 10–75 mg qd at night
Desipramine 10–75 mg/day qd at night
Venlafaxine 37.5–340 mg/day BID-TID

Question 48

Anticonvulsants and doses

Answer 48

Gabapentin 900–3600 mg/day TID
Pregabalin 150–600 mg/day BID–TID
Carbamazepine 100–1000 mg/day BID–QID

Question 49

Opioids and doses

Answer 49

Morphine (extended release) 15–60 mg BID–TID
Oxycodone (extended release) 10–60 mg BID–TID
Methadone 5–20 mg BID–TID

Question 50

calcitonin

Answer 50

provide pain relief in patients with CRPS. its analgesic properties are derived from the release of b-endorphins.

Question 51

Intrathecal Baclofen

Answer 51

CRPS can lead to dystonia often refractory
to standard treatment, and baclofen a GABA (type
B) receptor agonist that inhibits sensory input into the
spinal cord has been shown to be effective in some patients
with dystonia.

Question 52

Spinal Cord Stimulation

Answer 52

There is increasing evidence to support the value of spinal cord stimulation (SCS) in the
treatment of patients with CRPS who have experienced
suboptimal benefit from conventional therapy

Question 53

Functional Restoration

Answer 53

remains is the hallmark of successful treatment of CRPS. This is best
achieved in a multidisciplinary setting with the occupational
therapist initiating the early desensitization process and the physical therapist addressing muscle strength, flexibility, gait training, and overcoming the kinesophobia typically associated with advanced CRPS.

Question 54

In Functional Restoration
a recreational therapist may be involved in the later stages of restoration
to help

Answer 54

the patient return to socialization and engagement
in recreational activities that may have been neglected in
the course of the disease.

Question 55

Motor Imagery Program

Answer 55

A motor imagery program (MIP)
incorporates recognition of the limb laterality, imagined
movements, and mirrored movements using a mirror box
device

Question 56

Psychotherapy

Answer 56

Depression and anxiety commonly occur
in patients with chronic pain. This is amplified in CRPS as
a result of the uncertainty associated with the cause,
course, and treatment of the disorder

Question 57

post-traumatic stress disorder

Answer 57

The risk of developing
post-traumatic stress disorder is present in this patient population amid fears that the disease may progress or recur without warning. Instituting cognitive-behavioral therapy is the most effective psychological intervention found to produce long-lasting reduction in psychological symptoms in both children and adults with CRPS.