Physical Medicine and Rehabilitation for Complex Regional Pain Syndromes
- Author: Manish K Singh, MD; Chief Editor: Stephen Kishner, MD, MHA more...
Complex regional pain syndrome (CRPS) may develop as a disproportionate consequence of a trauma affecting the limbs without nerve injury (CRPS I, or reflex sympathetic dystrophy [RSD]) or with obvious nerve lesions (CRPS II, or causalgia). (See images below and Images 1-4.)
See the list below:
In the 17th Century, Ambroise Pare presented the earliest description of RSD as severe burning pain following peripheral nerve injury. Pare, a surgeon, treated King Charles IX for smallpox by inducing bleeding with a lancet applied to the arm. After this treatment, the king suffered from persistent pain, muscle contracture, and inability to flex or extend his arm.
In 1864, Mitchell coined the term causalgia, which means burning pain, to describe persistent symptoms following gunshot wounds to peripheral nerves during the American Civil War.
In 1900, Sudeck described radiographic spotty osteopenia.
In 1916, Leriche focused on the sympathetic nervous system.
In 1943, Livingston expanded the Leriche vicious circle theory that includes the following:
- Abnormally firing, self-sustaining loops in the dorsal horn
- Provoked by a small irritation focus in small nerve endings of major nerve trunks
- Activating central projecting fibers, giving rise to pain
In 1946, Evans used the term RSD, believing that sympathetic hyperactivity is involved somehow in the abnormal activity in the periphery.
In 1993, the International Association for the Study of Pain (IASP) held a Special Consensus Conference addressing diagnosis and terminology (endorsing the term CRPS).
In 1995, Paice wrote that, even after 130 years, there was still no general agreement on what to call RSD, what causes it, or how best to treat it. 
CRPS is a relatively common disabling disorder of unknown pathophysiology. RSD is a variable symptom complex that probably results from multiple causes arising through different pathophysiologic mechanisms. Changes in the peripheral and central somatosensory, autonomic, and motor processing and a pathologic interaction of sympathetic and afferent systems are described as underlying mechanisms.
Several hypotheses exist regarding the mechanism of sympathetically mediated pain and describe central and peripheral components. Wasner and colleagues demonstrated a complete functional loss of cutaneous sympathetic vasoconstrictor activity in an early stage of RSD/CRPS I, with recovery.  This autonomic dysfunction originates in the central nervous system (CNS).
Kurvers and colleagues suggested a spinal component to microcirculatory abnormalities at stage 1 of RSD, which appeared to manifest itself through a neural antidromic mechanism.  This spinal component may be evoked by traumatic excitation of a peripheral nerve on the affected side.
Baron and Janig have proposed a positive feedback circuit, consisting of primary afferent neuron, spinal cord neurons, sympathetic neurons, and a pathologic sympathetic coupling.
The cause of vascular abnormalities is unknown, and debate still surrounds the question of whether the sympathetic nervous system (SNS) is involved in the generation of these changes.
The old Sudeck concept of an exaggerated regional inflammatory response is supported by new data indicating that, in patients with acute RSD, immunoglobulin G labeled with indium-111 ( 111 In) is concentrated in the affected extremity.
A study with 31 P (phosphorus) nuclear magnetic resonance (NMR) spectroscopy showed an impairment of high-energy phosphate metabolism, which explains why these patients are unable, rather than unwilling, to exercise.
Electron microscope studies of skeletal muscle biopsies showed reduced mitochondrial enzyme activity, vesiculation of mitochondria, disintegration of myofibrils, abnormal depositions of lipofuscin, swelling of endothelial layers, and thickening of the basal membrane, which are all signs of oxidative stress. Oxygen consumption is reduced in limbs affected by RSD, and reduction of pain following treatment with oral vasodilators has been described.
After a partial nerve lesion, excessive antidromic activation of undamaged afferent C fibers and neuropeptide release, leading to acute vasodilation within the innervation territory of the affected nerve, were demonstrated.
The frequency of the presence of human lymphocyte antigen-DQ1 (HLA-DQ1) was increased significantly in RSD compared with control frequencies. This association provides an indication of an organic basis.
Because autoantibodies against nervous system structures have been described in these patients, Blaes and colleagues suggest an autoimmune etiology. 
Limited information is available about the epidemiology of CRPS in the United States and internationally. Actual incidence is unknown, as CRPS is often misdiagnosed. Some sources report, the incidence of causalgia (CRPS II) following injury to a peripheral nerve is 1-5%. The incidence of RSD (CRPS I) is 1-2% after various fractures and 2-5% after peripheral nerve injury.
RSD has significant morbidity, so raising awareness of this disease is important. According to Murray, earlier recognition and appropriate referral is very important, especially in children. Prompt referral can avoid unnecessary investigations and treatments that may worsen the condition.
RSD is reported more commonly in women. In a prospective study by Veldman and colleagues, which reviewed 829 patients, 628 patients were female (76%), and 201 were male (24%).
RSD may appear in every age group, but, as widely reported, it is less common in children aged less than 10 years. The lower apparent prevalence in children may be an artifact from underdiagnosis, perhaps due to a milder clinical course or a lower index of suspicion by the treating clinicians. In the Veldman study of 829 patients, age of diagnosis was 9-85 years (median 42 y); only 12 patients were younger than 14 years.
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