Complex Regional Pain Syndrome: Diagnosis and Treatment

August 1, 2006

A review of the diagnosis and treatment of complex regional pain syndrome (CRPS).

August 2006, Vol. XXIII, No. 9

In my previous column on complex regional pain syndrome (CRPS), I discussed the history and causes of the syndrome. As I noted in that column, what are now called CRPS types I and II were previously known as reflex sympathetic dystrophy and causalgia. In this column, I will review the diagnosis and treatment of CRPS. The diagnosis of CRPS is primarily based on the clinical presentation and history.

Classically, 3 stages of CRPS have been described: acute, dystrophic, and atrophic. The acute stage usually begins within weeks after a traumatic precipitating event and lasts up to 3 months. The primary symptoms are a burning type of pain and red, warm, edematous skin over the affected region. In the dystrophic stage, which lasts from 3 to 6 months, the pain may extend outside the original injured area. The skin becomes cool, mottled, and cyanotic, and a patchy osteoporosis, often described as a ground-glass appearance on x-ray films, may develop in the affected limb. In the atrophic stage, which can last for years, the pain is variable. The skin often takes on a pale, shiny appearance, and demineralization of the affected limb may be noted.

While allodynia (a painful response to a nonpainful stimulus) and hyperalgesia (an increased response to a normally painful stimulus) are not axiomatic for CRPS, when one or both is present, this diagnosis should certainly be considered.

The extended course of CRPS can be variable.1 Symptoms may improve, worsen, or remain the same. One of the interesting phenomena that has been observed in CRPS is that the symptoms can resolve even years after the onset of these disorders. Unfortunately, as yet, no clear predictive factors have been identified about the probable long-term outcome for the individual patient. It does appear that as for chronic pain in general, patients who maintain regularly scheduled activity tend to do better.2

The 3-phase bone scan is overall the best diagnostic test for identifying this disorder. It is considered suggestive of CRPS if increased pooling is present in the early bone-uptake phase. However, while this test appears to be relatively specific for CRPS, it is not an especially sensitive test for this disorder. 3 Thus, a negative result does not exclude a diagnosis.

Generally speaking, the earlier treatment for CRPS is started, the more likely it is that treatment will be successful.4

Unfortunately, many cases of CRPS are not correctly diagnosed until long after the onset of the initial symptoms. Thus, whenever the clinical presentation is suggestive of CRPS, aggressive treatment should be started.

Although it has been found that CRPS can be present in the absence of increased sympathetic activity, sympathetic ganglion blocks have been employed both diagnostically and therapeutically. Unfortunately, their efficacy appears to markedly decline after the acute stage of the disorder. Intravenous regional blocks with guanethidine have also been used with varying results, but this agent is no longer available in the United States. Transcutaneous electrical nerve stimulation units and acupuncture may provide pain relief and, since both have a benign side-effect profile, they should be considered.

At one time, surgery-most notably sympathectomy-was often performed on patients with CRPS. However, the results were found to be disappointing overall and the additional destruction of a portion of the nervous system carried the potential risk of irreversibly exacerbating the pain and other symptoms. Although CRPS pain can become so severe that patients may request amputation of the affected extremity, it is clear that this is not a viable alternative. Not only is it unlikely to provide relief, there is a marked possibility that amputation will exacerbate pain. Dielissen and associates5 reported that of 28 patients with CRPS type I who underwent amputation, 13 had increased pain.

Many different medications have been used in the management of CRPS.4 Unfortunately, there are limited controlled studies on which ones are most efficacious and none are FDA approved for the treatment of CRPS. Since it is considered to be a form of neuropathic pain, it is recommended that the medication management of CRPS be approached as for other types of this pain. Thus, antidepressants, anti-convulsants, and opioids would appear most likely to be effective.6

Among antidepressants, those that act on both the serotonergic and noradrenegic systems, such as the tricyclic antidepressants, venlafaxine (Effexor), and duloxetine (Cymbalta), are considered to be the most analgesic. Antidepressants are also beneficial for the depression that patients with chronic pain often suffer. The 2 anticonvulsants that are most commonly employed for the treatment of pain are gabapentin (Neurontin) and pregabalin (Lyrica).

Neuropathic pain syndromes also may respond to opioid analgesics. Since patients with CRPS usually report that they suffer from almost constant pain, longer-acting opioids, such as sustained- release morphine (MS Contin, Oramorph) and oxycodone (OxyContin), methadone (Dolophine, Methadose), and transdermal fentanyl (Duragesic), may provide more sustained relief than shorter-acting preparations.

More recently, there have been reports indicating that the N-methyl D-aspartate receptor antagonist and anesthetic agent ketamine (Ketalar, others) may be effective for the treatment of CRPS. Both oral and parenteral forms of this drug have been used. However, ketamine is associated with marked side effects, most notably psychosis. In one study, hallucinations developed in 6 of 33 patients with CRPS who were treated with a continuous infusion of ketamine.7

Spinal cord stimulation has also been reported to be beneficial, especially for CRPS type I, and should be considered as a treatment option if pharmacologic management is ineffective. 8 However, some CRPS experts have expressed dissatisfaction with this treatment both because of questions of long-term efficacy and the potential for side effects secondary to the wires becoming loose.9

The presence of CRPS can have a significant impact on patients' mental health, and can markedly impair functioning and severely disrupt patients' lives. Furthermore, because of the unusual nature of the pain and the ignorance about these disorders among the general public and even many health care providers, the suffering may be discounted. Because of all of these factors, CRPS patients often benefit from psychotherapy to help them cope with their problems and to maintain as high a level of functioning as possible. Group therapy with other CRPS patients may be useful because sufferers of this disorder, unlike those of the more widely known chronic pain disorders, are often unaware that there are others who have the same problems.

The severity of pain can lead to a reduction of the use of the affected extremity, resulting in atrophy. Favoring the painful body part may result in the development of pain in the contralateral side caused by overuse or poor body mechanics. Both physical therapy and occupational therapy focusing on daily activities can be of marked importance in preventing these problems.

Dr King is clinical professor of psychiatry at the New York University School of Medicine.


1. McBride A, Atkins R. Complex regional pain syndrome. Curr Orthop. 2005;19:155-165.
2. Yung Chung O, Bruehl SP. Complex regional pain syndrome. Curr Treat Options Neurol. 2003;5: 499-511.
3. Fournier RS, Holder LE. Reflex sympathetic dystrophy: diagnostic controversies. Semin Nucl Med. 1998;28:116-123.
4. Stanton-Hicks M. Complex regional pain syndrome: manifestations and the role of neurostimulation in its management. J Pain Symptom Manage. 2006;31:S20-S24.
5. Dielissen PW, Claassen AT, Veldman PH, Goris RJ. Amputation for reflex sympathetic dystrophy. J Bone Joint Surg Br. 1995;77:270-273.
6. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289-305.
7. Correll GE, Maleki J, Gracely EJ, et al. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 2004;5:263-275.
8. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006;10:91-101.
9. Kemler MA, de Vet HC, Barendse GA, et al. Spinal cord stimulation for chronic reflex sympathetic dystrophy-five-year follow-up. N Engl J Med. 2006; 354:2394-2396.