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Complex regional pain syndrome (CRPS), in the past known as reflex sympathetic dystrophy (RSD), is characterized by severe pain, swelling, skin color change, limited range of motion, vasomotor instability, and bone demineralization usually that affects the limbs.
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First was described in the sixteenth century by a French surgeon and barber; he described severe and persistent pain syndrome in the limbs after phlebotomy.1 In 1864, Silas Weir Mitchell reported a specific type of pain that resulted from penetrating wounds during the civil war, which was the first description of the syndrome in North America.1 In 1872, Mitchell named this finding with the term causalgia. Sudeck’s atrophy was described in 1900. He described posttraumatic bone atrophy. RSD was described by Evans in 1946.2
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After that, multiple articles were published with different names for the same presentation until 1993, when the International Association for the Study of Pain (IASP) reviewed the nomenclature and developed criteria. In 1994, a new nomenclature was developed, CRPS, noting that it is a complex disorder, which tends to begin in a region of the body, usually the distal aspect of an extremity, where the pain is a necessary component with a presentation of a variety of clinical symptoms.
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The etiology of CRPS is unknown, but it can be precipitated by trauma, including fractures, crush injuries, sprain, or surgery. In a retrospective study of 74 cases of CRPS, the most frequent reported etiologies were fractures (46%) and sprain (12%).3
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The pathophysiology of CRPS is not well known and seems to be multifactorial. Some proposed mechanisms include inflammation of deep tissue, neurogenic, and/or changes in pain perception in the Central Nervous System.4 A significant increase in proinflammatory cytokines IL-beta, IL-2, IL-6, and TNF-alfa occurs in the affected tissue, plasma, and CSF.5–8
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Marinus J et al. found that IL-8 elevated in the blood during the acute phase of CRPS. During the chronic phase, several proinflammatory mediators, including TNFα, interferon-γ (IFNγ), IL-2, monocyte chemoattractant protein-1 (MCP-1), and bradykinin increased. Also, IL-6, MCP-1, and macrophage inflammatory protein 1β (MIP-1β) were found in the affected limb.8
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With neurogenic inflammation, neuropeptides may be released, including substance P, neuropeptide Y, and calcitonin gene-related peptide. Pain can be explained on the basis of central sensitization, where the activity of nociceptive afferent signals increases.4 In a study by Birklein et al. of 145 patients with CRPS found that 97% of patients manifested motor dysfunction such as tremors, exaggerated reflexes, dystonia, and myoclonic jerks.9 However, a systematic review revealed that there was no notable change in the motor cortex of the affected limb.10 The sympathetic nervous system dysfunction plays a role in many chronic CRPS patients.11 Autonomic dysfunction can cause local or systematic manifestations like hyper or hypohidrosis, skin color changes, or differences ...