Understanding Complex Regional Pain Syndrome

To say the medical community’s knowledge of chronic pain is scant is something of an understatement. We still do not understand the etiology of most cases of many common chronic pain conditions, including low back pain and headaches. But of all the chronic pain syndromes we have identified by name, none is as misunderstood by physicians and patients alike as complex regional pain syndrome (CRPS) types I and II, the current names for symptom constellations previously called reflex sympathetic dystrophy (RSD) and causalgia, respectively. Our limited knowledge about this disorder, its etiology, and effective management means that patients who suffer what is frequently very severe pain often do not receive the correct diagnosis and do not receive appropriate treatment.

Many physicians are still relatively unfamiliar with this disorder even though the first in-depth description was made more than 150 years ago by the physician often considered the father of American neurology-S. Weir Mitchell. He and his colleagues observed soldiers wounded in the Civil War. They noted that some soldiers who were wounded in the hand or foot developed a burning pain that was exacerbated by touching the affected body part and persisted long after the wounds appeared to have healed. This syndrome was named causalgia, Greek for “burning pain.”

Similar conditions were described over the years and given a variety of names, including posttraumatic injuries, algodystrophy, and Sudeck atrophy. In 1953, John Bonica, one of the pioneers in the study of pain, suggested that these disorders be subsumed under the term "reflex sympathetic dystrophy.” The term proved confusing for the general public and so particularly problematic for patients who were given the diagnosis. Common understanding of a “reflex” is as a response to a hammer tap on the knee during a physical examination and the only type of “dystrophy” known to most people is the completely unrelated disease muscular dystrophy. “Sympathetic” carried no clinical meaning for friends or family of a patient with RSD but may perhaps have been taken to mean that people should receive sympathy for their suffering.

The validity of the term also was frequently questioned from a medical viewpoint. One of the major problems was uncertainty about the role of the sympathetic nervous system (SNS) in this disorder. The fact that there is a great deal of variability in response to sympathetic blocks suggests that in many patients the pain is not due to dysfunction of the SNS. Also, whether the syndrome is a reflex response to anything is open to question and not all patients develop dystrophic changes.

General confusion around the terms “RSD” and “causalgia” prompted the International Association for the Study of Pain in its 1994 classification of chronic pain to re-name these syndromes.¹ RSD became complex regional pain syndrome (CRPS) type I and causalgia CRPS type II. The difference between types I and II is that in the latter there is evidence of a definable nerve lesion. (The acronym CRPS is commonly pronounced “crips” rhyming with “chips.”)

Incidence
The incidence of CRPS is unclear. Patients with symptoms of CRPS frequently see a number of physicians before the correct diagnosis is made, so it appears that many cases are never diagnosed. CRPS type I especially may go unrecognized because of the absence of an identifiable peripheral nerve injury. CRPS almost always follows some form of trauma to the affected body part, usually an extremity. The trauma can range in severity from surgery to accidental injury to chronic overuse, all of which cause expected pain and so physicians may overlook the diagnosis.  

Using an electronic database and searching for patients with the diagnosis of CRPS or its synonyms and symptoms suggesting CRPS, Dutch researchers found an overall incidence rate of 26.2 new cases per 100,000 annually.² This translates into approximately 50,000 new cases per year in the United States. 

Studies that examined specific patient populations that had suffered traumatic injuries to extremities found CRPS to be fairly common. For example, a study of patients with fractures of the distal radius reported that 18% developed CRPS type I.³ Another study of 162 soldiers wounded in the Iraqi War who were seen in pain clinics reported that 4.3% suffered CRPS type II and 1.9%, CRPS type I.⁴ Because many patients with CRPS appear “normal” (ie, no overt signs of injury); because the pain often seems so bizarre (ie, out of apparent proportion to the nature of the original injury, lasting beyond when pain would have been expected to resolve); and because many health care professionals do not recognize signs and symptoms of the syndrome, patients may be mislabeled as either exaggerating their pain for secondary gain or even of malingering. One of the saddest things is that these patients may be stigmatized as falsifying their discomfort-by peers, by family and, unfortunately, by physicians. Even as a pain specialist, CRPS is the last pain disorder I would consider faking. To even begin to provide what would be even close to a valid story supporting the presence of CRPS would require knowledge of the disorder far beyond what most people, including most health care professionals, possess. 

Unknown etiology
What causes CRPS remains a mystery. Because it virtually always follows an injury of some kind, it would appear that some anatomic or physiologic change occurs. There does not appear to be any correlation, however, between the severity of the trauma and the development of the long-lasting and typically burning pain. In fact, the original injury may be nearly insignificant-for example, banging one’s hand or foot hard enough to cause acute pain but without suffering any apparent fracture or other marked injury. Nor have any reliable predictive factors for who will develop CRPS been discovered. It remains unknown whether there are changes at a level which we are not yet able to measure or whether there is something different about the people who develop the syndrome.
   
A variety of physiologic mechanisms have been proposed. The classic view that the pain is due to hyperactivity of the SNS has been discounted, although the SNS appears to be involved in some of the symptoms, most notably the edema, blood flow, and sudomotor changes. Currently, CRPS is believed to be the result of a combination of peripheral and central factors. Among the proposed peripheral mechanisms are an inflammatory process, peripheral sensitization, and changes in sodium channels.⁵ These processes may result in central changes, including an exaggerated response to peripheral input and a reduction of descending inhibitory pathways.

Because the severity of the original trauma often does not correlate with the level of ongoing pain reported by many CRPS patients, attention has often focused on the role of psychological factors in the development of the pain. Despite this speculation, there are no consistent findings of a correlation between preexisting mental health disorders and the development of CRPS. It has been proposed, however, that there may be brain changes, most notably in the primary sensory cortex, secondary to the CRPS and that these can lead to a distorted body image where patients perceive that the affected limb is larger than it actually is.^6,7 What role these changes may play in the pain and other symptoms of CRPS is still the subject of speculation.

Click here for Part II – Diagnosis and Management of CRPS References
1. Merskey H, Bogduk N, eds. International Association for the Study of Pain Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press; 1994.
The latest edition of the IASP classification is available here. 
2. de Mos M, de Bruijn AG, Huygen FJ, et al. The incidence of complex regional pain syndrome: a population-based study. Pain. 2007;129:12-20.
3. Puchalski P, Zyluk A. Complex regional pain syndrome type 1 after fractures of the distal radius: a prospective study of the role of psychological factors. J Hand Surg Br. 2005;30:574-580.
4. Cohen SP, Griffith S, Larkin TM, et al. Presentation, diagnoses, mechanisms of injury and treatment of soldiers injured in operation Iraqi freedom: an epidemiological study conducted at two military pain management centers. Anesth Anal. 2005;101:1098-1103.
5. Bruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010;113:713-725.
 6. Moseley GL. Distorted body image in complex regional pain syndrome. Neurology. 2005;65:773.
7. Birklein F, Rowbotham MC. Does pain change the brain? Neurology. 2005;65:666-667.