Complex Regional Pain Syndrome in Emergency Medicine

Updated: Sep 07, 2023
  • Author: Marcella L Ruffo, MD; Chief Editor: Andrew K Chang, MD, MS  more...
  • Print


A French surgeon by the name of Ambroise Paré described complex regional pain syndrome (CRPS) in the mid-16th century. [1]  Paré was the physician to French King Charles IX of Valois and went on to describe the condition after the King experienced an extreme burning pain in his arm after suffering from a smallpox infection. Paré noted other symptoms, including shortened arm muscles and the inability to stretch and bend the whole arm. Paré was also said to have identified the syndrome that we now refer to as phantom limb pain during his time as a military surgeon and his experiences with limb amputations. [2]  Physicians throughout the world have described similar syndromes over the centuries and CRPS has held many names, even just within the English language. 

CRPS, an entity formally called reflex sympathetic dystrophy (RSD), has readily identifiable signs and symptoms and is treatable if recognized early; however, the syndrome may become disabling if unrecognized. [3]  Emergency medicine physicians may be the first to see the syndrome and their actions can vastly improve the quality of life and functionality of these patients if treated properly. As a medical community, the description and management of this syndrome remain incomplete, however, vast improvements have been made over the past 30 years with increased research into the field. 



With complex regional pain syndrome (CRPS) being described by many in various forms, the consensus definition is that “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.” [4]  

Schwartzman stated that a common mechanism may be injury to central or peripheral neural tissue. [5] Roberts proposed that sympathetic pain results from tonic activity in myelinated mechanoreceptor afferents. Input causes tonic firing in neurons that are part of a nociceptive pathway. Campbell et al propose a hypothesis that places the primary abnormality in the peripheral nervous system. [6] More recent articles agree that the cause is still unknown. [7] Recent interest has focused on an immune-mediated mechanism. [8]

Most authors now agree that CRPS is a neurologic disorder affecting central and peripheral nervous systems. [9, 10] Mechanisms include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. [10, 11]

Other etiologic possibilities have been suggested. German research has noted the association between elevated levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and enhanced tumor necrosis factor-alpha activity in patients with polyneuropathy with allodynia. [12] Other German researchers have described autoantibodies in patients with CRPS, especially CRPS type 2. [13]

Harvard researchers Oaklander and Fields have proposed that distal degeneration of small-diameter peripheral axons may be responsible for the pain, vasomotor instability, edema, osteopenia, and skin hypersensitivity of CRPS-1. [14]

The recent association between the use of ACE inhibitors and CRPS has caused some to consider a neuroinflammatory pathogenesis. [15]

Research has demonstrated cortical changes, suggesting a possible role in pathophysiology. [16]

This complex syndrome has been further classified into two subtypes: 

  • Type I: No evidence of peripheral nerve injury (formerly reflex sympathetic dystrophy) 

  • Type II: Peripheral nerve injury present (formerly “causalgia”) 




CRPS occurs in approximately 1–15% of peripheral nerve injury cases. Schwartzman states that CRPS usually occurs secondary to fractures, sprains, and trivial soft tissue injury. [5] The incidence after fractures and contusions ranges from 10% to 30%. While some cases are associated with an identifiable nerve injury, many are not. Even "microtrauma" as might occur with an immunization may be responsible. The upper extremities are more likely to be involved than the lower.

Entities that have led to RSDS include the following:

A retrospective epidemiologic analysis of CRPS patients compared to patients with other pain disorders found an incidence of 13.6 per 100,000 per year. [17]


In and of itself, CRPS is not fatal. Morbidity of CRPS is associated with disease progress through a series of stages (see Physical).

Schwartzman et al reviewed questionnaires from 656 patients with CRPS. Once patients had experienced symptoms for more than one year, the majority of signs and symptoms were developed. No one reported spontaneous remission of symptoms. [18]


In a retrospective study of the Nationwide Inpatient Sample database from 2007 to 2011 in the United States, Elsharydah et al found that the patient population was primarily White. [19]  


Stanton-Hicks and others note that women predominate in a range of 60–80% of cases. [20]  Elsharydah et al also found that women continued to be the predominant sex affected by CRPS. [19]  It should be noted that CRPS can affect both sexes and occur at any age.


Persons of all ages are affected. Stanton-Hicks reports that in contrast to adults, 90% of pediatric cases occur in female children aged 8-16 years, with the youngest being 3 years. That author and others report that CRPS is treated most effectively in pediatric patients, with a remission rate of 97%. [21, 22]

An Israeli group suggested that CRPS in children and adolescents is underdiagnosed. They emphasize the importance of early recognition and multidisciplinary treatment. [23]

Several have looked into the possibility that there may be an increased risk of CRPS development in siblings. de Rooij et al showed that, although the overall risk is not increased, the risk in siblings younger than 50 years is significantly increased. [24, 25]



Prognosis of complex regional pain syndrome (CRPS) depends largely on timely diagnosis and use of early aggressive therapy. The ultimate outcome relies heavily on the severity of the original injury, age at onset or inciting event, and comorbidities such as smoking and diabetes. Some patients will continue to have disability, but this is becoming less common as the recognition of the disease is better understood. 


Patient Education

Patients should be encouraged to seek out complex regional pain syndrome (CRPS) support groups. The Reflex Sympathetic Dystrophy Syndrome Association has produced a user-friendly guideline document that may be helpful to both clinicians and patients. [9]