Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS) is a chronic progressive disease characterized by

severe pain, swelling and changes in the skin.
The cause of this syndrome is currently unknown.

Synonyms

Reflex Sympathetic dystropy in English speaking

Sudecks osteodystrophy in German speaking
Algo dystrophy in french speaking
Causalgia after nerve injury
Pour four du petit syndrome by anaesthetists
Peripheral trohoneurosis/Babinsky-forment sympathetic paralysis by neurologists
Leriche posttraumatic pain syndrome

Sympathic maintaince pain syndrome

Transient osteoperosis
Acute atrophy of bone
Shoulder-hand syndrome

History and Nomenclature

The earliest description of severe burning pain after peripheral nerve injury is that by the surgeon
Ambroise in the 17th century
Silas Weir Mitchell during the American Civil War, who is sometimes also credited for inventing
the name "causalgia." However, this term was actually coined by Mitchell's friend Robley
Dunglison from the Greek words for heat and for pain.
1900, Paul Sudeck described regional demineralization accompanying posttraumatic pain
In 1916, Leriche noticed improvement in causalgia patients after sympathectomy and proposed
that causalgia was caused by excessive activity of the sympathetic nervous system (SNS). He
also noted that sympathectomy could effect permanent relief.
1946, Evans introduced the term reflex sympathetic dystrophy. The term reflex sympathetic
dystrophy came into use to describe the condition, based on the theory that sympathetic
hyperactivity was involved in the pathophysiology.

1993, a special consensus workshop held in Orlando, Florida, provided the umbrella term
"complex regional pain syndrome," with causalgia and RSD as subtypes.

Epidemiology
Age common in younger adults
Mean 41.8 years
Mean age at time of injury 37.7 years
Mean duration of symptoms before pain center evaluation = 30 months
2.3 to 3 times more frequent in females than males
Usually involves a single limb in the early stage

Classification
The International Association for the Study of Pain has divided CRPS into two types based on
the presence of nerve lesion following the injury.
Type I, also known as reflex sympathetic dystrophy (RSD), Sudeck's atrophy, reflex
neurovascular dystrophy (RND) or algoneurodystrophy, does not have demonstrable nerve
lesions.
Type II, also known as causalgia, has evidence of obvious nerve damage.

Etiology
Triggered by a variety of events
Trauma (often minor) ranks as the leading provocative event
Ischemic heart disease and myocardial infarction
Cervical spine or spinal cord disorders
Cerebral lesions
Infections
Surgery
Repetitive motion disorder or cumulative trauma, causing conditions such as
carpal tunnel
In approximately 10% of patients, no precipitant can be identified

Activation of the sympathetic nervous system following an injury is part of a fright-flight response to an
emergency situation. This response is very important for survival. For example, firing of sympathetic
nerves causes blood vessels in the skin to contract, forcing blood deep into muscle and enabling the
victim to use his muscle to get up after an acute injury and escape from further danger. Also the decreased
supply of blood to the skin reduces blood loss through superficial injuries that may occur on the surface
of the body. Ordinarily, the sympathetic nervous system shuts down within minutes to hours after an
injury. For reasons we do not understand, individuals who go on to develop RSD / CRPS, the sympathetic
nervous system appears to assume an abnormal function. Theoretically, this sympathetic activity at the
site of injury could cause an inflammatory response causing the blood vessels to spasm leading to more
swelling and pain. (See B, C, and D in Figure 1) The events could lead to more pain which triggers
another response, establishing a vicious cycle of pain.

1943 Livingston- theory of reverbating circuts. He suggested that intense painful stimuli
indicated these circuits, which once established are excited by normal stimuli and are interpreted
centrally as pain
1944 Doupe et al- proposed pain due to activation of sensory fibers of sympathic efferents
1947 Nathan proposed artificial synapses are formed at site of lesion and allow emphatic
transmission between efferent and afferent fibers causing pain

1959 Drucker et al proposed that minuscule peripheral nerve twig could be damaged in soft
tissue injury & form artificial synapses in the same manner as majour nere trunks
1965 Melzack and Wall proposed gait-control theory of pain proposed cells of substantia
gelatinosa functions to modulate sensory input
1976 Sunderland proposed turbulence theory- injury to post ganglionic synaptic efferents caused
retrograde changes in sympathetic ganglion & trans synaptic degeneration in spinal cord causing
self sustained circuts

Clinical features
History
1. Symptoms develop following injury (usually symptoms begin within 2 months post injury).
2. Onset is in a single extremity.
3. Burning pain.
4. Hyperalgesia or allodynia (allodynia means pain elicited by stimuli that normally are not
painful, i.e., a patient reports severe pain in response to gentle stroking of the skin.).
5. Swelling.
6. Asymmetry or instability of temperature or color.
7. Asymmetry or instability of sweating.
8. Trophic changes of skin, nails, hair.
B. Findings by examination
1. Hyperalgesia or allodynia.
2. Edema (if unilateral and other causes excluded).
3. Vasomotor changes such as asymmetry or instability of temperature/color.
4. Sudomotor changes such as excess perspiration in affected extremity.
5. Trophic changes such as shiny skin, hair loss, abnormal nail growth.
6. Findings suggestive of impaired motor function such as:
(a) tremor.
(b) abnormal limb positioning.
(c) diffuse weakness that cannot be explained by neuralgic loss or by dysfunction of
joints, ligaments, tendons or muscles. Often the pain spreads to include the entire arm or
leg, even though the initiating injury might have been only to a finger or toe. Pain can
sometimes even travel to the opposite extremity. It may be heightened by emotional
stress.
Clinical Course
The clinical course of CRPS is divided into three stages,

Stage I CRPS
Stage I CRPS is characterized by mild symptoms and begins within days or weeks of the
precipitating injury. Sharp, burning pain, swelling, and dysfunction are localized, and although
mild in comparison to the later stages of CRPS, the symptoms are more serious than would
normally be expected for the injury. This exaggerated response is a key diagnostic factor when
dealing with possible cases of CRPS. Allodynia is generally absent during stage I, although
hyperesthesia is present, and the limb is relatively immobile and sensitive. Stage I (acute) may
last up to 3 months.
Stage II CRPS
Stage II is marked by increasing dysfunction and symptom severity and is defined by the
increased chronicity of the symptoms. Pain persists and increases in severity, as does sensitivity.
Changes to the distal portions of the affected limb reflect the growing autonomic dysfunction.
The limb is increasingly moist and cold, edema increases, and the skin becomes mottled.
Continued immobilization leads to increasing joint stiffness, and myofascial contractures are
possible. CRPS at stage II may respond to treatment, but often persists for several months. Stage
II (dystrophic) can last 3 to 12 months.
Stage III CRPS
Stage III is the most severe stage, where symptoms that have developed during stage II reach a
level of near intolerance. Stage III (atrophic) occurs from 1 year on. Severe aching and throbbing
pain is present, and the limb is effectively immobilized and functionally useless. Chronic
autonomic dysfunction leads to dystrophic changes to skin, muscle tissue, and bone tissue.
Halted growth of nails and hair accompanies dystrophic changes to the skin, muscles become
atrophied, and regional osteoporosis is observed on plain films and bone scans. At this stage, the
symptoms are unresponsive to treatment, and the condition is considered permanent.

Differential Diagnosis

Diabetic and small-fiber peripheral neuropathies

Entrapment neuropathies

Thoracic outlet syndrome

Discogenic disease

Deep vein thrombosis

Cellulitis

Vascular insufficiency

Lymphedema

Erythromelalgia

Investigations
Psychological and social factors are readily recognized issues in analyzing the
disorder. In patients with either CRPS I or II, there is a significant amount of
major psychiatric comorbidity. Major depressive disorder and personality
abnormalities are regularly found
Radiography has played a role in diagnosing this condition since Sudeck
described osteoporosis as part of the atrophic phase. Plain films may show
osteopenia in the affected limb.
Nucleotide bone scans or scintigraphy has become the preferred diagnostic test
to demonstrate dystrophic changes in bone, where increased uptake on the
affected side indicates CRPS-induced osteopenia.
Modified Sympathetic Blockade Testing

Most common test involves injecting a neural blockade and analyzing the response in the
affected limb. In such tests, normal saline solution is used as a control, and Novocaine (5%
procaine hydrochloride) is used as a pharmacologic neural blocker. The solution is injected
into either the stellate ganglion, when the arm is involved, or the lumbar paravertebral
ganglia, when the lower limbs are involved. Alternative neural blockade tests include
injection of guanethidine, an intravenously administered agent that depletes presynaptic
noradrenaline stores, thus producing an initial exaggeration of symptoms, followed by relief
in CRPS patients. Also, the phentolamine test may be administered, whereby adrenoreceptors
are blocked, and relief of symptoms and pain indicates increased peripheral sympathetic
activity

Treatment
Physical therapy
Facilitate movement of the affected region of the body

Pharmacologic management
Bisphosphonate-type compounds
Target the process of bone resorption
Outcome measures : Pain, motion, and tenderness were evaluated
Baclofen
Specific GABA-receptor (type B) agonist
Inhibits sensory input to the neurons in the spinal cord
Intrathecal administration of baclofen has been partially effective to treat the dystonia
associated with CRPS

 Adrenergic active drugs

Intravenous phentolamine : no significant pain relief and no significant worsening.
Increased pain with local injection of an adrenergic agonist in patients with longstanding
CRPS
Systemic steroids
30 mg/d of oral prednisone was significantly better than placebo.
Other therapies
Calcitonin : no benefit
Calcium channel blockers
Antidepressants : amitriptyline and imipramine neuropathic pain
Anticonvulsants :carbamazepine and phenytoin
NMDA-receptor antagonists Capsaicin
Thalidomide : cytokines might play a major role in the development of the CRPS syndrome

Invasive treatments include:

Tender point injections

Nerve stimulation
Epidural clonidine
Regional sympathetic nerve block
Ganglion blocks
Intravenous regional blocks
Dorsal column spinal cord stimulation
Sympathectomy

References
Campbells OPERATIVE ORTHOPAEDICS, 11th Edition
Rockhood & Greens Fractures in adults 7th edition
Reflex Sympathetic Dystrophy and Pain Dysfunctionin the Lower ExtremityBY THOMAS
N. LINDENFELD, M.An Instructional Course Lecture, The American Academy of
Orthopaedic Surgeons
The treatment of reflex sympathetic dystrophy syndrome J Bone Joint Surg Am.
1984;66:625-629.
Complex regional pain syndrome: manifestations and the role of neurostimulation in its
management.
J Pain Symptom Manage. 2006 Apr;31(4 Suppl):S20-4. Review.